effects hep b vax summary 508

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 ACIP BRIEFING MATERIALS FOR PUBLIC POSTING
 The Non -specific Effects of Hepatitis B Vaccines : A Rapid Systematic Revie w
Table of Contents
A. Background  ................................ ................................ ................................ ................................ ................................ ..... 3
B. Methods  ................................ ................................ ................................ ................................ ................................ ..........  3
B.1. Key Question Development  ................................ ................................ ................................ ................................ ..... 3
B.2. Literature Search  ................................ ................................ ................................ ................................ ......................  3
B.3. Study Selection ................................ ................................ ................................ ................................ .........................  4
B.4. Data Extraction, Study Assessment, and Synthesis  ................................ ................................ ................................ . 6
B.5. GRADE -ing and Recommendation Development  ................................ ................................ ................................ .... 6
C. Summary of Evidence  ................................ ................................ ................................ ................................ .....................  7
C.1. Evidence Tables  ................................ ................................ ................................ ................................ ........................  7
C.1.a. GRADE -ed Summary of Findings  ................................ ................................ ................................ ...........................  7
D. Extracted Evidence from Included Studies  ................................ ................................ ................................ ...............  14
E. Search Strategies and Results  ................................ ................................ ................................ ................................ ..........  21
F. References  ................................ ................................ ................................ ................................ ................................ ........  23

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 Table 1. PI/ECO(ST) Criteria for Key Question  ................................ ................................ ................................ .......................  3
Table 2. GRADE Table: Mortality and administration of monovalent hepatitis B vaccines in the first 6 years of life  .......  7
Table 3. GRADE Table: Mortality and administration of all hepatitis B -containing vaccines in the first 6 years of life ... 10
Table 4. GRADE Table: Cardiopulmonary outcomes and administration of hepatitis B vaccines in the first 6 years of life
 ................................ ................................ ................................ ................................ ................................ ..............................  14
Table 5. Characteristics of Studies Meeting Inclusion Criteria  ................................ ................................ ...........................  14
Table 6. Results of Studies Meeting Inclusion Criteria  ................................ ................................ ................................ ........  15
Table 7. Risk of Bias Assessment of Studies Meeting Inclusion Criteria  ................................ ................................ ............  19
Table 8. Primary Search of MEDLINE (OVID), Embase (OVID), CINAHL (Ebsco), Scopus, Cochrane Library  ......................  21

Figure 1. Results of the Study Selection Process  ................................ ................................ ................................ ...................  5

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 A. Background
Non -specific effects of vaccination include broader impacts that may be conferred by vaccines beyond protection against
their target pathogen, including the potential for effects on all -cause morbidity and mortality, non -targeted infections,
allergic and a topic disease, autoimmune and immune -mediated disease, and malignancy.1 While the non -specific effects
of certain vaccines, including Bacille Calmette -Guérin (BCG) vaccine, measles -containing vaccines, and diphtheria -
tetanus -pertussis vaccines, among others,1 have been previously studied, an evidence -based review of non-specific
effects associated with hepatitis B -containing vaccines is needed. Given the need to ensure the safety of all vaccination s
administered in childhood, we propose a systematic review of the literature to understand any non -specific effects of
childhood vaccinations. In this report, we focused on the literature that evaluated non -specific effects of hepatitis B
vaccination .
B. Methods
B.1. Key Question Development
The Key Question  was developed  by infectious disease and systematic review methodology subject matter experts
using the PICO  framework2 (Population, Intervention, Comparator, and Outcome ). The Key Question  and PI /ECO(ST)
Criteria  used to guide the literature review are:
1. What are the non -specific effects of childhood vaccines?
Table 1. PI/ECO(ST) Criteria for Key Question
PI/ECO(ST) ELEMENT  Description for this Review
Population  Infants and children through 6 years of  age
Intervention or
Exposure  Hepatitis A (HAV) – Havrix, VAQTA, Hepatitis B (HBV) – Recombivax HB, Engerix -B, Rotavirus
– ROTARIX, RotaTeq, Diphtheria, tetanus, acellular pertussis (DTaP) – Infanrix, Daptacel,
Haemophilus influenzae type B (Hib) – PedvaxHIB, ActHIB, Hiberix, Poliomyel itis/polio (IPV) –
IPOL, Pneumococcal (PCV15, PCV20) –VAXNEUVANCE, Prevnar 20, Measles, mumps rubella
(MMR) – PRIORIX, M -M-R II, Varicella - Varivax
RSV – Nirsevimab, Clesrovimab, Combination vaccines – Pediarix, Kinrix, Quadracel, Vaxelis,
Pentacel, ProQuad
Comparator (if
applicable)  Any or none
Outcome(s)  Non -specific effects, all -cause morbidity, all -cause mortality (death), non -targeted infection
(sepsis, respiratory tract), allergic and atopic disease (asthma, eczema, atopic dermatitis,
food allergy), autoimmune and immune -mediated disease (type 1 diabet es mellitus,
inflammatory bowel disease – ulcerative colitis and Crohn’s disease, juvenile idiopathic
arthritis, systemic lupus erythematosus, Hashimoto’s thyroiditis, alopecia), malignancy
(cancer, leukemia)
Setting  Any
Time Frame  Any publication years
Any duration of follow up

B.2. Literature Search
A CDC informationist (J T) developed search strategies from the Key Question s and PICO criteria,  and performed the
search in MEDLINE, EMBASE , CINAHL , and Cochrane Library  from  the start of each database to August  20, 2025 .
Search strategies and results are provided in  Table 8.

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 B.3. Study Selection
Results of the literature searches were uploaded into EndNote 21 (Clarivate Analytics©, Thomson Reuters, New
York, NY, USA), duplicate records were removed, and unique t itles and abstracts  were uploaded to Covidence
(Veritas Health Innovation Ltd., Melbourne, VIC, Australia) where a second round of deduplication was conducted.
As this was the first of several planned systematic  reviews on non -specific effects of childhood vaccination, a
keyword search was conducted to filter records with title and abstracts  relevant for hepatitis B vaccines (Hepatitis B,
HBV, HepB, Engerix -B, Recombivax HB, Pediarix, Vaxelis). Two reviewers (EQ, EM, BE ) independently screened all
titles and abstracts and removed irrelevant references. Relevant  full texts  were screened independent ly by two
reviewers  (EQ, LZ ) and disagreements were resolved by consensus . All studies were screened according to the pre -
identified exclusion criteria below, and results of the study selection process are provided in Figure 1 .

Criteria for excluding studies from the literature review include:
1. No full text  available;
2. Not available in English;
3. Not relevant to key question ;
4. No population of interest  (study popula tion did not include children vaccinated at ≤6 years of age ;
5. No intervention of interest  (no hepatitis B vaccine exposure) ;
6. No outcome of interest;
7. No primary data  or secondary data not systematically collected  (no reproducible methods) ; or
8. Insufficient me thodologic reporting (i.e., m eeting abstract  or poster );

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Figure 1. Results of the Study Selection Process

Disclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or
policy .  Page 6 of 24
 B.4. Data Extraction , Study Assessment , and Synthesis
Data from studies meeting inclusion criteria were independently extracted by two reviewers using a standardized Microsoft Excel (2021) form, and
differences were reconciled by discussion. Extracted data included study characteristics  (Table 5). Outcome data were extracted as presented in the studies
or calculated using data provided. For the purposes of this review, statistical significance was defined as p ≤ 0.05 . The risk of bias for each study was assessed
according to study type  using standardized  risk of bias tools  appropriate to the identified st udy type. Tools were modified to specify region, time, age ,
weight, and  prematurity, as  confounding factors  and to include an assessment of conflict -of-interest  disclosures . The Newcastle -Ottawa Scale was used for
cohort and case control studies , R.O.B2. for randomized controlled trials (RCTs) , and JBI tools were used to assess the risk of bias for Case Series and
Systematic Reviews . The signaling questions used to assess study conduct and risk of bias and results are presented in Table 6. The evidence was narratively
synthesized for  each  outcome domain, and for specific outcomes where definitions aligned.
B.5. GRADE -ing and Recommendation Development
The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach  was used to assess the  risk of bias , imprecision,
inconsistency, and indirectness , and final confidence for the body of evidence  foreach outcome .3

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policy .  Page 7 of 24
 C. Summary of Evidence
C.1. Evidence  Tables
C.1.a. GRADE -ed Summary of Findings
Key Question: Among children, what are the non-specific effects of hepatitis B vaccine s administered in the f irst 6 years of life ?
Table 2. GRADE Table: Mortality and administration of monovalent hepatitis B vaccines in the first 6 years of life
Outcome  Summary  Studies  Risk of Bias  Imprecision  Inconsistency  Indirectness  Confidence
All Mortality
Outcomes,
Monovalent
Hepatitis B
Vaccines  Evidence  from 3 cohorts  suggests hepatitis B vaccine
administration may  not be associated with an increase
in risk of mortality in high -income countries ( HIC) and
may be associated with an increase in risk in low-and
middle -income countries ( LMIC ). Two  studies from HIC
suggest  either a protective or no effect of hepatitis B
vaccination on mortality and one study from an LMIC
suggest s an increase in mortality  after hepatitis B
vaccination . Evidence  from 1 cohort and 1 nested case
series is inconsistent about  sex-specific mortality after
receipt of hepatitis  B vaccines; one study suggest s both
no difference and an increase in the female -to-male
mortality ratio and one study sugges ts no difference in
mortality by sex. One cohort suggest s either  a protective
or no effect on hepatitis B vaccines and cancer -related
and cardiovascular -related mortality.  4 Studies
(N=46,628)  Some concernsa No concerns  No concernsb Some
concernsc Very low
confidence
Mortality  Summary: The evidence from 2 cohort studies (He 2022
and Morgan 2025) in HIC suggests no association or a
decrease in mortality after hepatitis B vaccination. The
evidence from 1 cohort in Guinea -Bissau (Garly 2004)
suggests an increase in mortality after hepatitis B
vaccination; these findings had some concerns  for bias.   3 Cohorts
(He 2022,
Morgan
2025, Garly
2004)
(N=46,515)  Some concernsd No concerns  No concernse Some
concernsf Very low
confidence

a Confounding by weight/ weight -for-age z score  or health service utilization  in 2 studies, temporal  variation in 2 studies, regional differences in 2 studies,  concern for  exposure
misclassification in 1 study  and inadequate follow up in 1 stud y.
b Inconsistency may be explained by direct and indirect population differences .
c Aaby 2006 and Garly 2004 are conducted in LMIC population s.
d Confounding by weight/weight -for-age z score  or health service utilization  in 2 studies, temporal variation in 2 studies, regional differences in 2 studies, and inadequate follow
up in 1 stud y.
e Inconsistency may be explained by direct and indirect population differences .
f Garly 2004 is conducted in a LMIC population .

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policy .  Page 8 of 24
 Outcome  Summary  Studies  Risk of Bias  Imprecision  Inconsistency  Indirectness  Confidence
• One cohort (He, 2022) of 36,791 participants in
the National Health and Nutrition Examination
Survey in the United States suggested a
reduced risk of all -cause mortality associated
with hepatitis B vaccination [aHR 0.78 (95%CI:
0.68 -0.90); 390/10,785 PY vs  4,185/26,006 PY]
following vaccination  prior to 1.5 years of age
with a median follow -up of 8 years .
• One cohort (Morgan 2025) of extremely
preterm infants (<29 weeks gestation) in
Australia’s Surveillance of Adverse Events
Following Immunization in the Community
suggested there is no difference in risk of death
during the first 3 months of life when
compa ring infants with a record of receiving
hepatitis b vaccine within 24 hours of birth to
infants with no record of receiving hepatitis B
vaccine within 24 hours of life  [aRR: 1.13;
(95%CI: 0.42 -2.81); 7/306 vs 14/512].
• One cohort study (Garly 2004) of 8,906 children
from Bandim Health Project's Health and
Demographic Surveillance System in Guinea -
Bissau suggested increased mortality rate at 7 ½
- 12 months of age compared to mortality rate
at 1 ½ - 7 ½ months of age [aMR R: 1.62, 95% CI:
1.09, 2.41) for the birth cohort in which most
children received hepatitis B vaccination
(Hepaccine) at 7 ½ months of age. In a
subgroup analysis  within a measles vaccine
(MV) trial , mortality rate for children 7 ½ -12
months of age was ele vated among those
receiving hepatitis B vaccine (+MV) compared
to hepatitis B -unvaccinated (+MV) children
(5,441 children), [MRR 1.81 (95%CI: 1.19 -2.75)].
Hepaccine is not approved for use in the United
States.

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policy .  Page 9 of 24
 Outcome  Summary  Studies  Risk of Bias  Imprecision  Inconsistency  Indirectness  Confidence
Female and male
mortality  One cohort (Garly 2004) from Bandim Health Project's
Health and Demographic Surveillance System in Guinea -
Bissau  suggested elevated female -to-male (F/M)
mortality in a subgroup of 5,061 children ages, evaluated
through 12 and 24 months within a 2 -dose mea sles trial,
among those vaccinated for hepatitis B ( Hepaccine) 12
months: [F/M MRR 1.66 (95%CI: 0.80 -3.45); 18/143.8 PY
vs 12/159.1 PY] 24 months: [F/M MRR 2.20 (95%CI: 1.07 -
4.54); 22/358 PY vs 11/394.3 PY].

In a nested case series (Aaby 2006) in The Gambia’s
Medical Research Council  Laboratories’ Demographic
Surveillance System, hepatitis B vaccine was the last
vaccination received among 7% (4/60) of female infants
and 0% (0/53) male infants who died  and had vaccination
status available from 2 -17 months of age .   1 Cohort
(Garly 2004)
(N= 8,906)

1 Case
series
(Aaby 2006)
(N=113)  Some concernsg No concerns  No concerns  Some
concernsh Very l ow
confidence
Cancer -related
mortality  One cohort (He 2022) of 36,791 participants in the United
States’ National Health and Nutrition Examination Survey
suggested a trend toward reduction in cancer -related
mortality among people 6 years and older who had
received a hepatitis B vaccine compared to those who
were unvaccinated for hepatitis B [aHR 0.76 (95%CI: 0.58 -
1.00 ); 97/10,785 PY vs 881/26,006 PY ]. Most of the
vaccinated population had received hepatitis B vaccine in
the first 1.5 years of life  with a median follow -up of 8
years .
 1 Cohort

(He 2022)
(N=36,791)  No concerns  No concerns  No concerns  No concerns  Low confidence
Cardiovascular -
related mortality  One cohort (He 2022) of 36,791 participants in the United
States’ National Health and Nutrition Examination Survey
suggested no association between cancer -related
mortality in people 6 years and older and hepatitis B
vaccination [aHR 0.83 (95%CI: 0.60 -1.15 ); 53/10,785 PY vs
732/26,006 PY ]. Most of the vaccinated population had
received hepatitis B vaccine in the first 1.5 years of life
with a median follow -up of 8 years .
 1 Cohort

(He 2022)
(N=36,791)
 No concerns  No concerns  No concerns  No concerns  Low confidence

g Confounding by weight/weight -for-age z score or health service utilization and concern for exposure misclassification  in 1 study .
h Conducted in LMIC population .

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Table 3. GRADE Table: Mor tality  and administration of all hepatitis B -containing vaccines in the first 6 years of life
Outcome  Summary  Studies  Risk of Bias  Imprecision  Inconsistency  Indirectness  Confidence
All mortality
outcomes, all
hepatitis B -
containing vaccines  Evidence  from 4 cohorts is inconclusive about whether
receipt of a hepatitis B -containing vaccine is associated
with mortality . Studies  (n=2)  from HIC  suggest  a
protective or no effect of hepatitis B vaccination on
mortality and studies (n=2) from LMIC  suggest  an
increase in mortality  after hepatitis B vaccination.
Evidence  from 4 cohorts and 1 nested case series about
sex-specific mortality after hepatitis B -containing
vaccines varies . One cohort suggested either a
protective or no effect of hepatitis -B co ntaining vaccines
on cancer -related and cardiovascular -related mortality.
Findings may differ due to differences in types of
vaccines administered. Some studies evaluated
monovalent hepatitis -B vaccines , and some studies
evaluated pentavalent vaccines, which contain  antigens
to protect against diphtheria, tetanus, pertussis,
haemophilus  influenzae type B and hepatitis B.  8 Studies
(N=82,849)  Some
concernsi No concerns  No concernsj Some concernsk Very low
confidence
Mortality  Summary: The evidence from 2 cohort studies (He 2022
and Morgan 2025) in HIC suggests no increase in the risk
of mortality with hepatitis -B vaccination at a follow up of
3 months of life and a median follow up of 8 years of life .
• One cohort (He, 2022) of 36,791 participants in
the United States’ National Health and
Nutrition Examination Survey suggested a
reduced risk of all -cause mortality associated
with hepatitis B vaccination [aHR 0.78 (95%CI: 4 Cohorts
(He 2022,
Morgan
2025, Fisker
2018, Garly
2004)
(N=53,609)  Some concernsl No concerns  No concernsm Some concernsn Very low
confidence

i Confounding by weight/weight -for-age z score  or health service utilization  in 4 studies, temporal variation in 3 studies, regional differences in 2 studies, concern for exposure
misclassification in 1 study , outcome misclassification in 2 studies  and inadequate follow up in 1 stud y.
j Inconsistency may be explained by direct and indirect population differences
k Aamand 2023, Hanifi 2021, Fisker 2018, Fisker 2016, Aaby 2006, Garly 2004 are conducted in a LMIC population
l Confounding by weight/weight -for-age z score or health service utilization in 3 studies,  age at administration in 1 study,  temporal variation in 2 studies, regional differences in 2
studies, concern for outcome misclassification in 1 study and inadequate follow up in 1 stud y.
m Inconsistency may be explained by direct and indirect population differences
n Fisker 2018 and Garly 2004 are conducted in a LMIC population

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 Outcome  Summary  Studies  Risk of Bias  Imprecision  Inconsistency  Indirectness  Confidence
0.68 -0.90); 390/10,785 PY vs 4,185/26,006 PY]
following vaccination prior to 1.5 years of age
with a median follow -up of 8 years .
• One cohort (Morgan 2025) of extremely
preterm infants (<29 weeks gestation) in
Australia’s Surveillance of Adverse Events
Following Immunization in the Community
suggested there is no difference in risk of death
during the first 3 months of life when
compa ring infants with a record of receiving
hepatitis b vaccine within 24 hours of birth to
infants with no record of receiving hepatitis B
vaccine within 24 hours of life  [aRR: 1.13;
(95%CI: 0.42 -2.81); 7/306 vs 14/512].
Indirect  evidence from 2 cohort studies in Guinea -Bissau
(Fisker 2018, Garly 2004) suggests there may be  an
increase in  the risk of  mortality after  hepatitis -B
containing vaccination  (pentavalent and hepatitis B
vaccine ). There  are concerns about the generalizability of
LMIC infant mortality data to HIC infants.
• In on e cohort (Fisker 2018) in Guinea -Bissau,
pentavalent vaccine is administered at a
younger  age than measles vaccine.  7,094
infants in Bandim Health Project's Health and
Demographic Surveillance System suggested no
association between receiving  a measles
vaccine first and then a pentavalent vaccine
[aHR 1.19 (95%CI: 0.84 -1.69); 43/2,847 PY vs
160/14,186 PY], receiving missing pentavalent
doses [aHR 1.87 (95%CI: 0.96 -3.65); 10/430 PY
vs 160/14,186 PY] or not receiving missing
pentavalent doses [aHR 0.93  (95%CI: 0.57 -
1.54); 17/1,537 PY vs 160/14,186 PY] compared
to receipt of a  pentavalent vaccine first and
then a  measles vaccine.
• One cohort study (Garly 2004) of 8,906 children
from Bandim Health Project's Health and
Demographic Surveillance System in Guinea -
Bissau suggested increased mortality rate at 7

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policy .  Page 12 of 24
 Outcome  Summary  Studies  Risk of Bias  Imprecision  Inconsistency  Indirectness  Confidence
½ - 12 months of age compared to mortality
rate at 1 ½ - 7 ½ months of age [aMRR: 1.62,
95% CI: 1.09, 2.41) for the birth cohort in which
most children received hepatitis B vaccination
(Hepaccine) at 7 ½ months of age. In a
subgroup analysis  within a measles vaccine
(MV) trial , mortality rate for children 7 ½ -12
months of age was elevated among those
receiving hepatitis B vaccine (+MV) compared
to hepatitis B -unvaccinated (+MV) children
(5,441 children), [MRR 1.81 (95%CI: 1.19 -2.75)].
Hepaccine is not appro ved for use in the United
States.
Female -to-male
mortality  Summary: Indirect  evidence from 4 cohort studies in
LMIC  suggests there may be an increase in risk of
mortality among female compared to male  children
receiving hepatitis B vaccines. An increased female -to
male mortality rate was observed in 2 cohorts (Hanifi
2021, Fisker 2016) but not in 1 cohort (Aamand 2023).
One cohort in LMIC reported no difference in female to
male mortality at 12 months of age and an increase in
female mortality at 24 months  (Garly 2004).
• One cohort (Aamand 2023) of 12,753 infants in
Bandim Health Project's Health and
Demographic Surveillance System in Guinea -
Bissau suggested no association between
female and male mortality and pentavalent
vaccination [F/M aMRR 1.01 (95%CI: 0.82 -1.25);
73/2,901 PY vs 78/2,930 PY )] through 6 months
of follow -up post -vaccination .
• One cohort (Hanifi 2021) of 7,644 children ages
6 weeks - 9 months in the International Center
for Diarrheal Diseases Research Bangladesh’s 4 Cohorts
(Aamand
2023, Hanifi
2021, Fisker
2016, Garly
2004)
(N=38,033)

1 Case series
(Aaby 2006)
(N=113)
 Some
concernso Some  concernsp No concerns  Some concernsq Very low
confidence

o Confounding by weight/weight -for-age z score or health service utilization  in 2 studies  and concern for exposure misclassification  in 1 study and outcome misclassification in 1
study .
p Wide confidence intervals in the study reporting the highest female to male mortality differences .
q Conducted in LMIC population s.

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 Outcome  Summary  Studies  Risk of Bias  Imprecision  Inconsistency  Indirectness  Confidence
Health and Demographic Surveillance System
suggested elevated female -to-male mortality
after pentavalent vaccination [F/M MRR 9.91
(95%CI: 1.16 -84.44)].
• One cohort (Fisker 2016) of 8,730 infants in
Bandim Health Project's Health and
Demographic Surveillance System in Guinea -
Bissau suggested elevated female -to-male
mortality after pentavalent vaccination [F/M
aMRR 1.86 (95%CI: 1.16 -2.98), 52/1,939 PY vs
31/1,999 PY]  through 6 -months post -
vaccination .
• One cohort (Garly 2004) from Bandim Health
Project's Health and Demographic Surveillance
System in Guinea -Bissau suggested no
difference in  F/M mortality at 12 months [F/M
MRR 1.66 (95%CI: 0.80 -3.45); 18/143.8 PY vs
12/159.1 PY] and elevated F/M mortality at 24
months  [F/M MRR 2.20 (95%CI: 1.07 -4.54);
22/358 PY vs 11/394.3 PY]. after hepatitis B
vaccination ( Hepaccine)  in a subgroup of 5,061
children In a nested case series (Aaby 2006) in
The Gambia’s Medical Research Council
Laboratories’ Demographic Surv eillance
System, hepatitis B vaccine was the last
vaccination received by  7% (4/60) of female
infants and 0% (0/53) male infants who died
and had vaccination status information
available .
Cancer -related
mortality  One cohort (He 2022) of 36,791 participants in the United
States’ National Health and Nutrition Examination Survey
suggested a trend toward a reduction in  cancer -related
mortality among people 6 years and older who had
received a hepatitis B vaccin e compared to those who
were unvaccinated for hepatitis B  [aHR 0. 76 (95%CI: 0. 58-
1.00 ]. Most of the vaccinated population had received
hepatitis B vaccine in the first 1.5 years of life  with a
median follow -up of 8 years.
 1 Cohort

(He 2022 )
(N=36,791)
 No concerns  No concerns  No concern  No concerns  Low
confidence

Disclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or
policy .  Page 14 of 24
 Outcome  Summary  Studies  Risk of Bias  Imprecision  Inconsistency  Indirectness  Confidence
Cardiovascular -
related mortality   One cohort (He 2022) of 36,791 participants in the
United States’ National Health and Nutrition Examination
Survey suggested  no association between cancer -related
mortality in people 6 years and older and hepatitis B
vaccination [aHR 0.83 (95%CI: 0.60 -1.15] . Most of the
vaccinated population had received hepatitis B vaccine in
the first 1.5 years of life  with a median follow -up of 8
years .
 1 Cohort

(He 2022 )
(N=36,791)
 No concerns  No concerns  No concerns  No concern s Low
confidence

Table 4. GRADE Table: Cardiopulmonary outcomes and administration of hepatitis B vaccines in the first 6 years of life
Outcome  Summary  Studies  Risk of Bias  Imprecision  Inconsistency  Indirectness  Confidence
Cardiopulmonary  The evidence from 1 cohort suggests that receipt of hepatitis
B vaccine in the first 24 hours of life is not associated with an
increase in the risk of bronchopulmonary dysplasia.   1 Stud y
(N=818) Som e
concerns  No concerns
 No concerns
 No concerns
 Low
confidence

Bronchopulmonary
dysplasia  One cohort (Morgan 2025) of extremely preterm infants (<29
weeks gestation) in Australia’s Surveillance of Adverse Events
Following Immunization in the Community suggested there is a
reduction in risk of bronchopulmonary dysplasia when
comparing preterm infants  with a record of receiving hepatitis
b vaccine within 24 hours of birth to preterm  infants with no
record of hepatitis B vaccine within 24 hours of birth [aRR:
0.83; (95%CI: 0.68 -1.0); 155/306 vs 317/512].
 1 Cohort

(Morgan
2025 N =
818)  No concerns  No concerns  No concerns  No concerns  Low
confidence

D. Extracted Evidence from Included Studies
Table 5. Characteristics of Studies Meeting Inclusion Criteria
Author
Year  Study
design  Data Collection
Period  Vaccine  Sample size, N  Surveillance System (if Applicable)  Country
Aaby 20064 Nested case
series  1998 -2002  Hepatitis B [unspecified
manufacturer]  113 children who had died  and
had vaccination status  Medical Research Council  Laboratories'
Demographic Surveillance  System in Farafenni  The Gambia

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 Author
Year  Study
design  Data Collection
Period  Vaccine  Sample size, N  Surveillance System (if Applicable)  Country
Aamand
20235 Cohort  September 1, 2008 –
December 31, 2017  Pentavalent *  12,753 children  Bandim Health Project's Health and
Demographic Surveillance System  Guinea -Bissau
Fisker
20166 Cohort  September 1, 2008  –
April 18, 2011  Pentavalent * 8,730 children  Bandim Health Project's Health and
Demographic Surveillance System  Guinea -Bissau
Fisker
20187 Cohort  September 1, 2008 –
June 22, 2015  Pentavalent *  7,094 children
 Bandim Health Project's Health and
Demographic Surveillance System  Guinea -Bissau
Garly 20048 Cohort  March 1994 – February
2000  Hepatitis B (Hepaccine)  8,906 children  Bandim Health Project's Health and
Demographic Surveillance System   Guinea -Bissau
Hanifi
20219 Cohort  June 29, 2011 – April
20, 2016  Pentavalent * 7,644 children  International Center for Diarrheal Diseases
Research Bangladesh's Health and Demographic
Surveillance System in Chakaria  Bangladesh
He 202210 Cohort  1999 – 2018  Hepatitis B  [Unspecified
manufacturer,
thimerosal -free]  36,791 participants  National Health and Nutrition Examination
Survey  United States
Morgan
202511 Cohort  January  1, 2017 –
December  31, 2020  Hepatitis B  [Engerix -B
or HB -Vax-II,
thimerosal -free]  818 extremely preterm infants  Surveillance of Adverse Events Following
Immunization in the Community  Australia
*Pentavalent vaccine : Diphtheria -Tetanus -whole cell Pertussis -Hemophilus influenzae type B -Hepatitis B
Table 6. Results of Studies Meeting Inclusion Criteria
Study  Study
Type  Exposure  Outcome  Follow -up Outcome
Identification  Intervention
% or rate
(n/N  or
person -time ) Control %  or
rate  (n/N or
person -time)  p-
value  Measure of
Association
(95% CI)  Adjusted  Risk of
Bias
Aaby 2006  Nested
case
series  Hepatitis B as
last vaccin e Female d eath s Vaccination
through 18
months of age  Verbal autopsy  7% (4/60)  NA NA NA No High risk
of bias
Aaby 2006  Nested
case
series  Hepatitis B as
last vaccine  Male deaths  Vaccination
through 18
months of age  Verbal autopsy  0% (0/53) NA NA NA No High risk
of bias

Disclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or
policy .  Page 16 of 24
 Study  Study
Type  Exposure  Outcome  Follow -up Outcome
Identification  Intervention
% or rate
(n/N  or
person -time ) Control %  or
rate  (n/N or
person -time)  p-
value  Measure of
Association
(95% CI)  Adjusted  Risk of
Bias
Aamand
2023  Cohort  Pentavalent
vaccination  Female/male
mortality  Vaccination
through 6
months post -
vaccination  Reported
cause of death  25.5 per 1,000
person -years
(73/2,901 PY)  26.6 per 1,000
person -years
(78/2,930 PY)  NR 1.01 (0.82 -
1.25)  Yes Low risk of
bias
Fisker 2016  Cohort  Pentavalent
vaccination  Female/male
mortality  Vaccination
through either
Subsequent
vaccination
contact or 6
months post -
vaccination  Verbal
autopsy,
medical review  26.8 per 1,000
PY (52/1,939
PY) 15.5 per 1,000
PY (31/1,999
PY) 0.01  1.86 (1.16-
2.98) Yes Moderate
risk of bias
Fisker 2018  Cohort  Pentavalent
after measles
vaccine  Mortality  First home visit
after 9 months
to 5 years of
age Interview  15.1 per 1,000
PY (43/2,847
PY) 11.3 per 1,000
PY (160/14,186
PY) NR 1.19 (0.84 -
1.69)  Yes High risk
of bias
Fisker 2018  Cohort  Received
missing
Pentavalent
vaccine  at
most recent
visit Mortality  First home visit
after 9 months
to 5 years of
age Interview  23.3 per 1,000
PY (10/430 PY)  11.3 per 1,000
PY (160/14,186
PY) NR 1.87 (0.96 -
3.65)  Yes High risk
of bias
Fisker 2018  Cohort  Did not
receive
missing
pentavalent
vaccine  at
most recent
visit Mortality  First home visit
after 9 months
to 5 years of
age Interview  11.1 per 1,000
PY (17/1 ,537
PY) 11.3 per 1,000
PY (160/14,186
PY) NR 0.93 (0.57 -
1.54)  Yes High risk
of bias
Garly 2004  Cohort  7 ½ - 12 vs 1 ½
- 7 ½ months
of age, cohort
receiving
hepatitis B
vaccine
(Hep accine)  Mortality  1.5 months
through 12
months of age  Death
registration
system
 NR NR 0.03
 1.62 (1.09 -
2.41)
 Yes Moderate
risk of bias

Disclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or
policy .  Page 17 of 24
 Study  Study
Type  Exposure  Outcome  Follow -up Outcome
Identification  Intervention
% or rate
(n/N  or
person -time ) Control %  or
rate  (n/N or
person -time)  p-
value  Measure of
Association
(95% CI)  Adjusted  Risk of
Bias
Garly 2004  Cohort  Hepatitis B
vaccination
(Hepaccine)  Mortality  1.5 months
through 12
months of age  Death
registration
system
 nr/876  nr/4565  NR 1.81 (1.19 -
2.75)  No Moderate
risk of bias

Garly 2004  Cohort  Hepatitis B
(Hepaccine) +
measles
vaccine vs
measles
vaccine  Female/male
mortality  7 ½ months
through 12
months of age  Death
registration
system  12.5%
(18/143.8 PY)  7.5% (12/159.1
PY) NR 1.66 (0.80 -
3.45)  No Moderate
risk of bias
Garly 2004  Cohort  Hepatitis B
(Hepaccine)  +
measles
vaccine vs
measles
vaccine  Female/male
mortality  9 months
through 24
months of age  Death
registration
system
 6.1% (22/358
PY) 2.8% (11/394.3
PY) 0.04  2.20 (1.07 -
4.54)  No Moderate
risk of bias
Hanifi 2021  Cohort  Pentavalent
vaccination  Female/male
mortality  6 weeks
through 9
months of age  Household
visit 14.3 per 1,000
PY (9/618 PY)  1.4 (1/667 PY)  0.01  9.91 (1.16 -
84.44)  Yes High risk
of bias
He 2022  Cohort  Hepatitis B
vaccination
[Unspecified
manufacturer,
thimerosal
free All-cause mortality  Median follow -
up of 8 years  NHANES
Linked
Mortality File ,
1999 -2018  2.8%
(390/10,785)  11.8%
(4,185/26,006)  NR 0.78 (0.68 -
0.90)  Yes Low risk of
bias
He 2022  Cohort  Hepatitis B
vaccination
[Unspecified
manufacturer,
thimerosal
free Cancer -related
mortality  Median follow -
up of 8 years
 NHANES
Linked
Mortality File
1999 -2018
 0.7%
(97/10,785)  2.6%
(881/26,006)
 NR 0.76 (0.58 -
1.00)  Yes Low risk of
bias

He 2022  Cohort  Hepatitis B
vaccination
[Unspecified
manufacturer, Cardiovascular -
related mortality  Median follow -
up of 8 years
 NHANES
Linked
Mortality File ,
1999 -2018
 0.4%
(53/10,785)  1.9%
(732/26,006)  NR 0.83 (0.60 -
1.15)  Yes Low risk of
bias

Disclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or
policy .  Page 18 of 24
 Study  Study
Type  Exposure  Outcome  Follow -up Outcome
Identification  Intervention
% or rate
(n/N  or
person -time ) Control %  or
rate  (n/N or
person -time)  p-
value  Measure of
Association
(95% CI)  Adjusted  Risk of
Bias
thimerosal
free]
Morgan
2025  Cohort  Hepatitis B
vaccine within
24 hours of
birth  (Engerix -
B and H -B-Vax
II, thimerosal -
free)  All-cause mortality  Birth to 3
months  Victorian
Deaths Index
data set  2.3%
(7/306 ) 2.7%
(14/512 ) 0.87 1.13 (0.42 -
2.81)  Yes Some
concerns
Morgan
2025  Cohort  Hepatitis B
vaccine within
24 hours of
birth
(Engerix -B and
H-B-Vax II,
thimerosal -
free)  Bronchopulmonary
dysplasia  Birth to 3
months  ICD-10 50.7%
(155/306 ) 61.9%
 (317/512 ) NR 0.83 (0.68 -
1.00) Yes Some
concerns

Disclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or
policy .  Page 19 of 24
 Table 7. Risk of Bias Assessment of Cohort Studies Meeting Inclusion Criteria
STUDY NAME  Aamand 2023  Fisker 2016  Fisker 2018  Hanifi 2021  He 2022  Garly 2004  Morgan 2025
SIGNALING QUESTION  Cohort  Cohort  Cohort  Cohort  Cohort  Cohort  Cohort
Selection
Were the groups similar and recruited from the same population?  Yes  Yes  Yes  Yes  Yes  Yes  Yes
Were exposures/ interventions measured similarly to assign patients/
people?  Yes  Yes  Yes  Yes  Yes  Yes  Yes
Was the intervention/ exposure measured in a valid & reliable way?  Yes  Yes  Yes  Unclear  Yes  Yes  Yes
Comparability/ Confounding
Comparability of groups on basis of design or analysis  study controls/ adjusts for region  study controls/ adjusts for region  study controls/ adjusts for region  study controls/ adjusts for region  study controls/ adjusts for region  study does not control/ adjust for region  study does not control/ adjust for region
Comparability of groups on basis of design or analysis  study controls/ adjusts for time period  study does not control/ adjust for time period  study controls/ adjusts for time period  study controls/ adjusts for time period  study does not control/ adjust for time period  study controls/ adjusts for time period  study does not control/ adjust for time period
Comparability of groups on basis of design or analysis  study controls/ adjusts for weight  study controls/ adjusts for weight  study does not control/ adjust for weight  study does not control/ adjust for weight  study does not control/ adjust for weight  study does not control/ adjust for weight  study controls/ adjusts for weight
Comparability of groups on basis of design or analysis  study does not control/ adjust for prematurity  study does not control/ adjust for prematurity  study does not control/ adjust for prematurity  study does not control/ adjust for prematurity  study does not control/ adjust for prematurity  study does not control/ adjust for prematurity  study controls/ adjusts for prematurity
Comparability of groups on basis of design or analysis  study controls/ adjusts for age at administration  study controls/ adjusts for age at administration  study does not control/ adjust for age at administration  study controls/ adjusts for age at administration  study controls/ adjusts for age at administration  study controls/ adjusts for age at administration  study controls/ adjusts for age at administration
No residual confounding concerns exist  Yes  No No Unclear  Yes  No No
Outcome
Were the subjects free of the outcome of interest at the start of the
study?  Yes  Yes  Yes  Yes  Yes  Yes  Yes
Were the outcomes measured in a valid and reliable way?  Unclear  Yes  No No Yes  Yes  Yes
Was the same method of ascertainment or assessment of outcome
done for both groups?  Yes  Yes  Yes  Yes  Yes  Yes  Yes
Was the non -response rate similar across both groups?  Not applicable  Not applicable  Not applicable  Not applicable  Not applicable  Unclear  Not applicable
Follow up
Was the follow up time reported and long enough for outcomes to
occur?  Yes  Yes  Yes  Yes  Yes  Yes  Unclear
Was follow up complete, and if not, were the reasons for loss to follow
up described and explored?  Yes  Yes  Yes  Unclear  Yes  Unclear  Yes
Were strategies to address incomplete follow up utilized?  Yes  Yes  Yes  Yes  Not applicable  Yes  Not applicable
Analysis
Were appropriate statistical analyses used?  Yes  Yes  Yes  Yes  Yes  Yes  Yes
COI
Were conflicts of interest disclosed and no obvious conflicts exist?  Yes  Yes  Yes  Yes  Yes  No Yes
Risk -of-bias judgement  Low risk of bias  Some concerns  High risk of bias  High risk of bias  Low risk of bias  Some concerns  Some concerns
 Legend: Green = Yes or Possibly Yes, Yellow = Unclear, Red = No or Possibly No, Grey or Black = Not applicable

Disclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or
policy .  Page 20 of 24
 Table 8. Risk of Bias Assessment of Case Series Studies Meeting Inclusion Criteria
STUDY NAME  Aaby 2006
SIGNALING QUESTION  Nested case series
Selection
Were there clear criteria for inclusion in the case series?  Yes
Was the condition measured in a standard, reliable way for all
participants included in the case series?  Possibly Yes
Were valid methods used for identification of the condition for
all participants included in the case series?  Possibly No
Did the case series have consecutive inclusion of
participants?  Yes
Did the case series have complete inclusion of participants?  No Information
Was there clear reporting of the demographics of the
participants in the study?  No
Was there clear reporting of clinical information of the
participants?  No
Were the outcomes or follow up results of cases clearly
reported?  No Information
Was there clear reporting of the presenting site(s)/clinic(s)
demographic information?  No Information
Analysis
Were appropriate statistical analyses used?  Yes
COI
Were conflicts of interest disclosed and no obvious conflicts
exist?  Possibly Yes
Risk -of-bias judgement  High risk of bias
 Legend: Green = Yes or Possibly Yes, Yellow = Unclear, Red = No or Possibly No, Grey or Black = Not applicable

Disclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or
policy .  Page 21 of 24
 E. Search Strategies and Results
Table 9. Primary Search of MEDLINE (OVID), Embase (OVID), CINAHL (Ebsco), Scopus, Cochrane Library
Search Strategy:
DATABASE  STRATEGY  RUN DATE  RECORD
COUNT
Medline
(OVID)
1946 - 1. 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).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. Exp Safety/ OR exp Treatment Outcome/
8. (safety OR (vaccin* ADJ2 safe*) OR treatment outcome* OR adverse* OR harm OR harmful OR harms OR side effect* OR
reaction*).ti,ab,kf. OR ae.fs
9. 7 OR 8
10. Exp Clinical Study/ OR exp Product Surveillance, Postmarketing/
11. (trial* OR observational stud* OR observation stud* OR clinical stud* OR surveillance OR reporting system* OR VAERS OR
postmarket* OR post -market*).ti,ab,kf,hw.
12. 10 OR 11
13. 3 AND 6 AND 9 AND 12  07/31/2025  599
Embase
(OVID)
1947 - 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).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. Exp Safety/ OR exp Treatment Outcome/ OR adverse drug reaction/
8. (safety OR (vaccin* ADJ2 safe*) OR treatment outcome* OR adverse* OR harm OR harmful OR harms OR side effect* OR
reaction*).ti,ab,kf. OR ae.fs
9. 7 OR 8
10. Exp Clinical Study/ OR exp Postmarketing Surveillance/
11. (trial* OR observational stud* OR observation stud* OR clinical stud* OR surveillance OR reporting system* OR VAERS OR
postmarket* OR post -market*).ti,ab,kf,hw.
12. 10 OR 11
13. 3 AND 6 AND 9 AND 12
14. limit 13 to "pubmed/medline"
15. 13 NOT 14
16. limit 15 to conference abstract status
17. 15 NOT 16  07/31/2025  1527

-
DUPLICATES

=165
UNIQUE
RECORDS

Disclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or
policy .  Page 22 of 24
 DATABASE  STRATEGY  RUN DATE  RECORD
COUNT
Cochrane
Library
 #1 [mh "Hepatitis B Vaccines"]
#2 ((("Hepatitis B":ti,ab,kw OR HepB:ti,ab,kw OR "Hep B":ti,ab,kw OR HBV:ti,ab,kw) NEAR/5 vaccin*:ti,ab,kw) OR HepB -
BD:ti,ab,kw OR Engerix -B:ti,ab,kw OR "Recombivax HB":ti,ab,kw)
#3 #1 OR #2
#4 [mh Infant]
#5 (Infant*:ti,ab,kw OR newborn*:ti,ab,kw OR ("new" NEXT born*):ti,ab,kw OR neonat*:ti,ab,kw OR birth:ti,ab,kw OR birth -
dose*:ti,ab,kw)
#6 #4 OR #5
#7 [mh Safety] OR [mh "Treatment Outcome"]
#8 (safety:ti,ab,kw OR (vaccin*:ti,ab,kw NEAR/2 safe*:ti,ab,kw) OR ("treatment" NEXT outcome*):ti,ab,kw OR
adverse*:ti,ab,kw OR harm:ti,ab,kw OR harmful:ti,ab,kw OR harms:ti,ab,kw OR ("side" NEXT effect*):ti,ab,kw)
#9 #7 OR #8
#10 [mh ^"Clinical Study"] OR [mh ^"Product Surveillance, Postmarketing"]
#11 (trial*:ti,ab,kw OR ("observational" NEXT stud*):ti,ab,kw OR ("observation" NEXT stud*):ti,ab,kw OR ("clinical" NEXT
stud*):ti,ab,kw OR surveillance:ti,ab,kw OR ("reporting" NEXT system*):ti,ab,kw OR VAERS:ti,ab,kw OR
postmarket*:ti,ab,kw OR post -market*:t i,ab,kw)
#12 #10 OR #11
#13 #3 AND #6 AND #9 AND #12
 07/31/2025  400

-
DUPLICATES

=145
UNIQUE
RECORDS
CINAHL
(EBSCOHost)  S1 (MH "Hepatitis B Vaccines+")
S2 ((((TI "Hepatitis B" OR AB "Hepatitis B" OR SU "Hepatitis B") OR (TI HepB OR AB HepB OR SU HepB) OR (TI "Hep B" OR AB
"Hep B" OR SU "Hep B") OR (TI HBV OR AB HBV OR SU HBV)) N5 (TI vaccin* OR AB vaccin* OR SU vaccin*)) OR (TI HepB -BD
OR AB HepB -BD OR SU He pB-BD) OR (TI Engerix -B OR AB Engerix -B OR SU Engerix -B) OR (TI "Recombivax HB" OR AB
"Recombivax HB" OR SU "Recombivax HB"))
S3 S1 OR S2
S4 (MH Infant+)
S5 ((TI Infant* OR AB Infant* OR SU Infant*) OR (TI newborn* OR AB newborn* OR SU newborn*) OR (TI "new born*" OR AB
"new born*" OR SU "new born*") OR (TI neonat* OR AB neonat* OR SU neonat*) OR (TI birth OR AB birth OR SU birth) OR
(TI birth -dose* OR AB birt h-dose* OR SU birth -dose*))
S6 S4 OR S5
S7 (MH Safety+) OR (MH "Treatment Outcomes+") OR (MH "Adverse Drug Event+")
S8 ((TI safety OR AB safety OR SU safety) OR ((TI vaccin* OR AB vaccin* OR SU vaccin*) N2 (TI safe* OR AB safe* OR SU safe*))
OR (TI "treatment outcome*" OR AB "treatment outcome*" OR SU "treatment outcome*") OR (TI adverse* OR AB
adverse* OR SU adverse*) OR (TI harm OR AB harm OR SU harm) OR (TI harmful OR AB harmful OR SU harmful) OR (TI
harms OR AB harms OR SU harms) OR (TI "side effect*" OR AB "side effect*" OR SU "side effect*"))
S9 S7 OR S8
S10 (MH "Clinical Study+") OR (MH "Product Surveillance, Postmarketing+")
S11 ((TI trial* OR AB trial* OR SU trial*) OR (TI "observational stud*" OR AB "observational stud*" OR SU "observational stud*")
OR (TI "observation stud*" OR AB "observation stud*" OR SU "observation stud*") OR (TI "clinical stud*" OR AB "clinical
stud*" OR S U "clinical stud*") OR (TI surveillance OR AB surveillance OR SU surveillance) OR (TI "reporting system*" OR AB 07/31/2025  22

-
DUPLICATES

=7
UNIQUE
RECORDS

Disclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or
policy .  Page 23 of 24
 DATABASE  STRATEGY  RUN DATE  RECORD
COUNT
"reporting system*" OR SU "reporting system*") OR (TI VAERS OR AB VAERS OR SU VAERS) OR (TI postmarket* OR AB
postmarket* OR SU postmarket*) OR (TI post -market* OR AB post -market* OR SU post -market*))
S12 S10 OR S11
S13 S3 AND S6 AND S9 AND S12

Limiters  - Exclude  MEDLINE  records

F. References

1. Pittet L, Netea MG, Curtis N. Chapter 3 - Non -specific Effects of Vaccines. In: Stanley A. Plotkin WAO, Paul A. Offit, and Kathryn M. Edwards, ed. Plotkin's
Vaccines . 8 ed. Elsevier; 2023:37 -44.e7:chap 3.
2. Hosseini M -S, Jahanshahlou F, Akbarzadeh MA, Zarei M, Vaez -Gharamaleki Y. Formulating research questions for evidence -based studies. Journal of
Medicine, Surgery, and Public Health . 2024/04/01/ 2024;2:100046. doi: https://doi.org/10.1016/j.glmedi.2023.100046
3. Guyatt G, Agoritsas T, Brignardello -Petersen R, et al. Core GRADE 1: overview of the Core GRADE approach. Bmj. Apr 22 2025;389:e081903.
doi:10.1136/bmj -2024 -081903
4. Aaby P, Jensen H, Walraven G. Age -specific changes in the female -male mortality ratio related to the pattern of vaccinations: An observational study
from rural Gambia. Vaccine . 29 May 2006;24(22):4701 -4708. doi:10.1016/j.vaccine.2006.03.038
5. Aamand T, Fisker AB, Correia C, Fernandes M, Clipet -Jensen C, Thysen SM. Do Pentavalent (DTwP -Hib-HBV) vaccines have sex -differential nonspecific
effects? An observational study. Observational Study
Research Support, Non -U.S. Gov't. Hum Vaccin Immunother . 12 15 2023;19(3):2288297. doi:10.1080/21645515.2023.2288297
6. Fisker AB, Biering -Sorensen S, Lund N, et al. Contrasting female -male mortality ratios after routine vaccinations with pentavalent vaccine versus measles
and yellow fever vaccine. A cohort study from urban Guinea -Bissau. Research Support, Non -U.S. Gov't. Vaccine . 08 31 2016;34(38):4551 -4557.
doi:10.1016/j.vaccine.2016.07.034
7. Fisker AB, Thysen SM. Non -live pentavalent vaccines after live measles vaccine may increase mortality. Research Support, Non -U.S. Gov't. Vaccine . 10 01
2018;36(41):6039 -6042. doi:10.1016/j.vaccine.2018.08.083
8. Garly ML, Jensen H, Martins CL, et al. Hepatitis B vaccination associated with higher female than male mortality in Guinea -Bissau: An observational
study. Pediatr Infect Dis J . December 2004;23(12):1086 -1092. doi:10.1097/01.inf.0000145700.77286.94
9. Hanifi SMA, Biering -Sorensen S, Jensen AKG, Aaby P, Bhuiya A. Penta is associated with an increased female -male mortality ratio: cohort study from
Bangladesh. Research Support, Non -U.S. Gov't. Hum Vaccin Immunother . 01 02 2021;17(1):197 -204. doi:10.1080/21645515.2020.1763084

Disclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or
policy .  Page 24 of 24
 10. He WQ, Guo GN, Li C. The impact of hepatitis B vaccination in the United States, 1999 -2018. Hepatology . 06 2022;75(6):1566 -1578.
doi:10.1002/hep.32265
11. Morgan HJ, Nold MF, Kattan GS, et al. Hepatitis B vaccination of preterm infants and risk of bronchopulmonary dysplasia: a co hort study, Australia.
Vaccination contre l'hepatite B de prematures et risque de dysplasie bronchopulmonaire: etude de cohorte en  Australie, Vacunacion contra la hepatitis B en
neonatos prematuros y riesgo de displasia broncopulmonar: estudio de cohortes en Australia. Bull World Health Organ . 2025;103(3):187 -193.
doi:10.2471/BLT.24.291683

Summary: Disclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not  be construed to represent any agency determination or policy .  Page 1 of 24   ACIP BRIEFING MATERIALS FOR PUBLIC POSTING    The Non -specific Effects of Hepatitis B Vaccines : A Rapid Systematic Revie w  Table of Contents   A. Background  ................................ ................................…


02 langer hep b 508

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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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

Summary: 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…