CLINICAL PRACTICE GUIDELINE

No. 342, April 2017

Hepatitis B and Pregnancy

This Clinical Practice Guideline has been prepared by the Gina Ogilvie, MD, Vancouver BC
Infectious Diseases committee, reviewed by the Family
Caroline Paquet, RM, Trois-Rivires QC
Physician Advisory, Clinical Practice e Obstetrics and
Guideline Management and Oversight Committees and Vanessa Poliquin, MD, Winnipeg MB
approved by the Board of the Society of Obstetricians and Julie van Schalkwyk, MD, Vancouver BC
Gynaecologists of Canada.
Mark H. Yudin (chair), MD, Toronto ON
PRINCIPAL AUTHORS
Disclosure statements have been received from all members
Eliana Castillo, MD, Calgary AB of the committee(s).
Kellie Murphy, MD, Toronto ON Competing interests: None declared.
Julie van Schalkwyk, MD, Vancouver BC

GUIDELINE COMMITTEE
Abstract
Victoria Allen, MD, Halifax NS
Objective: To review the epidemiology, natural history, evaluation, and
Celine Bouchard, MD, Quebec QC treatment of hepatitis B virus (HBV) infection during pregnancy. This
Marc Boucher, MD, Montral QC will aid obstetric care providers in counseling their patients
regarding perinatal risks and management options available to
Isabelle Boucoiran, MD, Montral QC
pregnant women with hepatitis B.
Sheila Caddy, MD, Calgary AB
Outcomes: Outcomes evaluated include thresholds for HBV anti-viral
Eliana Castillo, MD, Calgary AB treatment for prevention of perinatal transmission and for invasive
Logan Kennedy, RN, Toronto ON procedures during pregnancy for women with hepatitis B infection.

Deborah Money, MD, Vancouver BC
Kellie Murphy, MD, Toronto ON
Key Words: Hepatitis B, antiviral therapy, breast-feeding, chronic
hepatitis, immuno- prophylaxis, vertical transmission, viral load,
pregnancy
http://dx.doi.org/10.1016/j.jogc.2016.11.001
J Obstet Gynaecol Can 2016;-(-):-e-
Copyright 2016 Published by Elsevier Inc. on behalf of The Society of
Obstetricians and Gynaecologists of Canada/La Socit des
obsttriciens et gyncologues du Canada
Evidence: Medline, EMBASE, and CINAHL were searched for articles in
English on subjects related to HBV infection, pregnancy, and perinatal
transmission from 1966 to March 2016. Results were restricted to
systematic reviews, randomized controlled trials/controlled clinical
trials, and observational studies. Other (unpublished) literature was
identied through searching the websites of health technology
assessment and health technology assessment-related agencies,
clinical practice guideline collections, clinical trial registries, and
national and international medical speciality societies.
Validation methods: The quality of the evidence is rated using the
criteria described in the Report of the Canadian Task Force on
Preventive Health Care (Table 1). Recommendations for practice
are ranked according to the method described in this Report.
Guideline update: The guideline will be reviewed 5 years after
publication to decide if an update is required. However, if important
new evidence is published prior to the 5-year cycle, the review
process may be accelerated for a more rapid update of some
recommendations.

This document reects emerging clinical and scientic advances on the date issued, and is subject to change. The information should not be
construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate amendments to these opinions.
They should be well documented if modied at the local level. None of these contents may be reproduced in any form without prior written
permission of the publisher.
Women have the right and responsibility to make informed decisions about their care in partnership with their health care providers. In order to
facilitate informed choices, women should be provided with information and support that is evidence based, culturally appropriate, and tailored to
their needs. The values, beliefs, and individual needs of each woman and her family should be sought and the nal decision about the care and
treatment options chosen by the woman should be respected.

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CLINICAL PRACTICE GUIDELINE

Table 1. Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force on
Preventive Health Care
Quality of evidence assessmenta Classication of recommendationsb
I: Evidence obtained from at least one properly randomized A. There is good evidence to recommend the clinical preventive
controlled trial action
II-1: Evidence from well-designed controlled trials without B. There is fair evidence to recommend the clinical preventive
randomization action
II-2: Evidence from well-designed cohort (prospective or retrospective) C. The existing evidence is conicting and does not allow to make a
or case-control studies, preferably from more than one centre or recommendation for or against use of the clinical preventive action;
research group however, other factors may inuence decision-making
II-3: Evidence obtained from comparisons between times or places D. There is fair evidence to recommend against the clinical
with or without the intervention. Dramatic results in uncontrolled preventive action
experiments (such as the results of treatment with penicillin in the E. There is good evidence to recommend against the clinical
1940s) could also be included in the category preventive action
III: Opinions of respected authorities, based on clinical experience, L. There is insufcient evidence (in quantity or quality) to make a recom-
descriptive studies, or reports of expert committees mendation; however, other factors may inuence decision-making
a
The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on Preventive
Health Care.
b
Recommendations included in these guidelines have been adapted from the classication of recommendations criteria described in The Canadian Task Force on
Preventive Health Care.

Sponsors: This guideline was developed with resources funded by the 4. Hepatitis B surface antigen-positive pregnant women should
Society of Obstetricians and Gynaecologists of Canada receive counseling on prevention of hepatitis B virus transmission
to sexual partners and household contacts. (II-2A)
Recommendations
5. If hepatitis B surface antigen is negative but there is an ongoing
1. Pregnant women should be offered screening for hepatitis B virus
risk of infection (e.g., born in country where hepatitis B virus is
infection in early pregnancy by determination of their hepatitis B
endemic, illicit drug use, multiple sexual partners, multiple trans-
surface antigen. (I-A)
fusions, immunosuppression, hepatitis B positive partner, health
2. If status of hepatitis B surface antigen is unknown at time of care workers, incarceration, or abnormal alanine aminotrans-
maternal admission to hospital, this should be done immediately to ferase), screening should be repeated in late pregnancy.3 (II-3A)
inform infant management.1,2 (III-A)
6. Women at high risk for acquiring hepatitis B infection who are hep-
3. Hepatitis B surface antigen-positive pregnant women require atitis B surface antigen-negative and have not been vaccinated for
testing for hepatitis B envelope antigen, hepatitis B virus (HBV) hepatitis B must be counseled on risk factor modication and should
DNA level, alanine aminotransferase (I-A) and ultrasound of the be offered recombinant hepatitis B vaccine series: pregnancy is not a
liver (III-B) during pregnancy for the purposes of maternal health contraindication for immunization to hepatitis B virus. (II-2A)
and perinatal HBV transmission risk stratication. A specialist
7. Encourage non-invasive screening techniques for aneuploidy prior
referral is recommended. (III-L)
to invasive testing for women who are hepatitis B surface antigen-
positive and counsel women that risk of transmission in utero in-
creases if maternal hepatitis B virus DNA is > 200 000 IU/mL
(> 106 copies/mL) at the time of amniocentesis. (II-2B)
ABBREVIATIONS
8. If possible, avoid intrapartum invasive procedures (e.g., fetal
ALT alanine aminotransferase electrocardiogram, scalp lactate) that may increase the infants risk
anti-HBe hepatitis B envelope antibody of percutaneous hepatitis B virus exposure. (III-L)
anti-HBs hepatitis B surface antibody 9. Cesarean section is not recommended for the sole purpose of
reducing the risk of perinatal transmission of hepatitis B virus. (II-2C)
CHB chronic hepatitis B
10. Vaccinate the neonate for hepatitis B and give hepatitis B immu-
CI condence interval noglobulin within the rst 12 hours of life to all neonates born to
DNA deoxyribonucleic acid women who are hepatitis B surface antigen-positive. (I-A)
FDA Food and Drug Administration 11. Breastfeeding does not pose an additional risk of hepatitis B virus
infection, even without neonatal vaccination, hence mothers with
GA gestational age
chronic hepatitis B infection who wish to breastfeed should be
HAV hepatitis A virus encouraged to do so. (II-2A)
HBeAg hepatitis B envelope antigen 12. Encourage families to complete the infant immunization series for
HBIG hepatitis B immunoglobulin hepatitis B virus according to local infant vaccination schedule and
obtain serological conrmation of protection after completion of hep-
HBsAg hepatitis B surface antigen atitis B vaccination series, no sooner than 9 to 12 months of age. (I-A)
HBV hepatitis B virus 13. In collaboration with an adult infectious diseases/gastroenterology or
HCC hepatocellular carcinoma hepatology specialist, consider antiviral treatment for viral suppres-
sion for prevention of perinatal transmission in women with hepatitis
HIV human immunodeciency virus
B DNA viral loads level > 200 000 IU/mL (> 106 copies/mL), starting
PEP post-exposure prophylaxis at 28 to 32 weeks GA and continuing until delivery. (II-B)

2 l - JOGC - 2016
 Hepatitis B and Pregnancy

GENERAL CONSIDERATIONS Table 2. Interpretation of hepatitis B serologic test

resultsa
Serologic

H BV is an enveloped DNA virus. It has an outer

envelope component of HBsAg and an inner
nucleocapsid component of hepatitis B core antigen.
markers
HBsAgb
Result
Negative
Interpretation
Susceptible to HBV
anti-HBcc Negative
HBeAg is typically measurable in serum when active viral anti-HBsd Negative
replication occurs. HBV DNA can be detected in serum HBsAg Negative Immune to HBV due to natural
and is used to monitor the degree of viral replication. Virus anti-HBc Positive infection
anti-HBs Positive
mutations that prevent HBeAg expression can develop,
HBsAg Negative Immune to HBV due to hepatitis
even when high viral loads exist, making HBeAg an un-
anti-HBc Negative B vaccination
predictable marker for HBV DNA level. Up to 30% of anti-HBs Positive
those with chronic infection may have such a mutation.4 HBsAg Positive Acute Infection
There are at least 10 different genotypes of HBV. anti-HBc Positive
Although some types are associated more often with dis- IgM anti-HBce Positive
anti-HBs Negative
ease progression, all types of HBV respond to antiviral
HBsAg Positive Chronic Infection
therapy, and HBV immunization is thought to be protec- anti-HBc Positive
tive against all genotypes. IgM anti-HBc Negative
anti-HBs Negative

EPIDEMIOLOGY HBsAg Negative Four possible interpretations:

Prevalence rates of HBV infection vary widely based on the
global geographical region. Prevalence rates are greater than
5% in sub-Saharan Africa, East Asia, the Pacic Islands, and
the Amazon Basin of South America. Almost half of the
worlds population lives in areas of high endemicity.5
In Canada, the rate of CHB in the general population is
less than 1%. However, among certain Canadian pop-
ulations such as adults from Southeast Asia, prevalence
may approach 5% to 15%.6 HBsAg prevalence was re-
ported at 0.4% in the 1990s in one Canadian province7 and
in almost one percent in a recent study from British
Columbia.8 In this latter study, 18% of HBsAg-positive
pregnant women were found to have active infection (i.e.,
were also HBeAg positive). Seven neonatal transmissions
were documented within this cohort, six of whom were
from mothers documented as HBeAg positive. All seven
infants received appropriate newborn HBV PEP.8 Even
though the majority (> 90%) of infants born to HBsAg-
positive women in Canada receives HBIG and more than
80% receive three doses of HBV vaccine, perinatal trans-
mission has been reported for about 1% to 2% of infants
who receive appropriate newborn HBV PEP.7
NATURAL HISTORY
Following transmission, HBV infects the liver and causes
inammation and hepatocellular necrosis. The mechanism by
which the virus infects hepatocytes is not well understood.
Once infection occurs, the clinical course varies from
subclinical disease to acute hepatitis or fulminant infection,
anti-HBc Positive 1. Resolved infection (most common)
anti-HBs Negative 2. False-positive anti-HBc, thus
susceptible
3. Low level chronic infection
4. Resolving acute infection
a
Hepatitis B serologic testing involves measurement of several HBV-specic
antigens and antibodies. This is used to identify different phases of HBV
infection and to determine the existence of acute or chronic HBV infection,
immunity to HBV as a result of prior infection or vaccination, or susceptibility to
infection.1
b
HBsAg: A protein on the surface of HBV; it can be detected in high levels in
serum during acute or chronic HBV infection. The presence of HBsAg indicates
that the person is infectious. The body normally produces antibodies to HBsAg
as part of the normal immune response to infection. HBsAg is the antigen used
to make hepatitis B vaccine.
c
Total hepatitis B core antibody (anti-HBc): Appears at the onset of symptoms
in acute hepatitis B and persists for life. The presence of anti-HBc indicates
previous or ongoing infection with HBV in an undened time frame.
d
Anti-HBs:The presence of anti-HBs is generally interpreted as indicating
recovery and immunity from HBV infection. Anti-HBs also develops in a person
who has been successfully vaccinated against hepatitis B.
e
Immunoglobulin (IgM) antibody to anti-HBc:Positivity indicates recent infection
with HBV (< 6 mos).
which may result in death.9 CHB, which occurs in 5% to
90% of those acutely infected, is dened as being HBsAg
positive for more than six months. It is conrmed with
persistence of HBsAg and the absence of anti-HBs, which
is a neutralizing antibody that can be detected after HBV
infection has been cleared or after successful HBV im-
munization. Anti-HBs and HBsAg, essentially, do not exist
together. HBeAg is generally considered to be a marker of
HBV replication and infectivity. It is usually associated with
high levels of HBV DNA in serum. Clearance of HBeAg
and seroconversion to anti-HBe occurs early in patients
with acute infection, well before clearance of HBsAg.
However, HBeAg seroconversion may be delayed for years

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CLINICAL PRACTICE GUIDELINE
Figure 1. Natural history of HBV infection acquired
during infancy
to decades in patients with chronic HBV infection
(Table 2).
It is estimated that up to two billion people have been
infected with HBV, and there are currently 240 million
individuals worldwide with CHB.5 Of those with CHB,
20% to 30% will develop complications including cirrhosis
or hepatocellular carcinoma. Each year, approximately 650
000 people die due to CHB. Ethnicity plays a role in dis-
ease progression; those of African descent have higher
rates of developing HCC and do so at a younger age.10
The degree of chronicity with HBV infection is inversely
proportional to the age at which the virus was acquired. In
absence of PEP, if infected as a newborn, the likelihood of
chronic infection is 90% (Figure 1). Chronic infection oc-
curs in 20% to 60% of cases if infection occurs under the
age of ve and in < 5% if infected as adults11,12; most
infections acquired during adulthood (w95%) do not
progress to chronic infection and resolve within a year
(Figure 2).
MODE OF TRANSMISSION
HBV is highly infectious, being 100 times more infectious
than HIV after a needle-stick exposure.13 The risk of
acquiring HBV from a needle-stick injury ranges from 1%
to 6% (source patient HBsAg-positive, HBeAg-negative) to
22% to 40% (source patient HBsAg-positive, HBeAg-
positive).14 HBV is transmitted by percutaneous (i.e.,
puncture through the skin) or mucous membrane exposure
to infected blood and, to a lesser degree, to other body
uids15; HBV can also survive up to seven days on envi-
ronmental surfaces. Vertical transmission (mother to child)
is the most common route of HBV transmission, but it can
also be transmitted by having sex with an infected partner,
injection drug use, contact with blood or open sores of
4 l - JOGC - 2016
Figure 2. Natural history of HBV infection acquired
during adulthood
an infected person, needle-sticks or sharp instrument ex-
posures, and sharing items such as razors or toothbrushes
with an infected person. HBV is not spread through food
or water, sharing eating utensils, breastfeeding, hugging,
kissing, hand holding, coughing, or sneezing.15
Perinatal transmission is the predominant mode of trans-
mission in high-prevalence areas. Horizontal transmission
(i.e., child to child) in early childhood accounts for most
cases of CHB in intermediate prevalence areas.16 Unpro-
tected sexual intercourse and intravenous drug use in
adults are the major routes of spread in low-prevalence
areas like Canada.16
TREATMENT AND PREVENTION
At the present time, there is no denitive cure for HBV
infection. The goal of CHB treatment is to decrease he-
patocyte histological damage by achieving sustained sup-
pression of viral replication and, by doing so, to prevent
progression to cirrhosis, end-stage liver disease, HCC, and
possibly death. Currently, the most effective strategy for
reducing HBV-related disease and death is through its
prevention by immunization. Newborn and childhood
immunization have signicantly reduced transmission;
however, where available, immunization programs have
been in existence for only a few decades. As such, the
protective effect of immunization on the global burden of
HBV will be recognized only in time.
CONSIDERATIONS IN PREGNANCY
Overall, pregnancy is not known to alter the natural history
of HBV infection and HBV infection is not associated with
increased risks of adverse pregnancy outcomes (except for
acute HBV infection in pregnancy e see below).

Figure 3. Risk of mother to child transmission according
to maternal viral load
PERINATAL TRANSMISSION
Perinatal transmission remains the most common form of
transmission of hepatitis B worldwide,17 and despite the
availability of neonatal PEP, almost 70% of global births
remain at risk of hepatitis B infection.17
Perinatal transmission can occur in-utero or through the
process of labor and birth. Although the exact mechanism
of each of these modes of transmission is unknown, the
majority of perinatal transmission occurs predominantly at
or after birth based on the high protective efcacy of
neonatal PEP (see below). In the absence of PEP, perinatal
transmission occurs in > 90% of deliveries where the
mother is HBeAg positive and in 15% of deliveries if the
mother is HBeAg negative.
The combination of HBIG and HBV immunization given
within 12 hours of birth has effectively reduced the rate of
perinatal transmission from > 90% to < 10%.11,18
Despite appropriate neonatal PEP, perinatal transmission
still occurs in approximately 2% of infants.19,20 Most of
these cases occur in HBeAg-positive women with very high
viral loads, generally > 200 000 IU/mL (> 106 copies/
mL).21e23
Several factors increase the risk of perinatal transmission,
such as maternal HBeAg, high HBV DNA viral loads,
resistant virus, HBV genotype, and incomplete or off
schedule PEP.24,25 HBV DNA level is the strongest single
risk factor driving perinatal transmission, even in the
setting of appropriate neonatal PE.23,26 Even after
adjusting for several other factors, maternal viral load re-
mains the strongest predictor of perinatal transmission at
an adjusted odds ratio of 3.49 for each log10 copy/ml in-
crease on maternal HBV viral load.27 Reported rates of
Hepatitis B and Pregnancy
perinatal transmission have been 0% at maternal viral load
< 106 copies/mL (200 000 IU/mL), 3.2% for 106-6.99
copies/mL (105-106 IU/mL), 6.6% for 107 copies/mL,
7.6% to 14.6% for 108 copies/mL (> 107 IU/mL) and
27.7% for 109 copies/mL, respectively (Figure 3).21,27
Antepartum transmission is rare but may occur with
antepartum haemorrhage, placental abruption, or threat-
ened preterm labour.28 Perinatal transmission has also
been associated with amniocentesis if maternal HBV DNA
is over 107 copies/mL.29 The mechanism for in-utero
HBV transmission is unknown, but HBV is found in the
villous capillary endothelial cells30 and the trophoblasts of
the placenta, supporting the hypothesis that breach of the
placental barrier is a mechanism for intra-uterine infection.
ACUTE HBV INFECTION DURING PREGNANCY
Acute hepatitis B infection during pregnancy usually results
in a mild maternal illness and is not associated with
increased fetal mortality or teratogenicity. However,
increased incidence of low birth weight and prematurity
has been reported.31,32 Perinatal transmission rate in the
setting of acute HBV is 10% if maternal infection happens
early in the pregnancy,32 but increases to 60% if maternal
infection occurs at or near the time of delivery.33
ASSESSMENT OF HBV INFECTION IN PREGNANCY
The most common scenario that obstetric care providers
encounter is an asymptomatic pregnant woman found to
be HBsAg positive on prenatal laboratory investigations. In
the absence of recent exposure or any symptoms of acute
hepatitis, most of these cases will represent a chronic rather
than acute HBV infection. Obstetric care providers should
arrange for HBeAg, anti-HBe, HBV DNA level, ALT, and
ultrasound of the liver for all HBsAg-positive pregnant
patients and arrange for specialist referral (see below) for
the purposes of maternal health and perinatal HBV
transmission risk stratication. In rural and remote areas in
Canada where referral is not feasible or possible, expert
advice should be obtained by phone or telehealth.
Referral to an adult hepatologist or infectious disease
specialist is recommended for all newly diagnosed CHB
infections, including those diagnosed during pregnancy.
Only 20% of pregnant women with CHB receive appro-
priate specialist care within a year after pregnancy.34
Newly diagnosed CHB infections require assessment for
other causes of liver disease, co-infections, and complica-
tions such as cirrhosis and HCC (see Table 3 for recom-
mended investigations). CHB-related cirrhosis and portal
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CLINICAL PRACTICE GUIDELINE
Table 3. Recommended investigations for patients with a
new diagnosis of CHB including pregnant women
HBeAg and antibody status (anti-HBe, an indirect marker of lower
levels of viraemia and infectivity)
HBV DNA level (quantitative direct measure of level of viraemia and
infectivity)
IgM antibody to hepatitis B core antigen (evidence of recent infection
with HBV)
Hepatitis C virus antibody, hepatitis delta virus antibody, HIV
antibody, HAV antibody
ALT, g-glutamyltransferase, serum albumin, total bilirubin, total
globulins, full blood count, and prothrombin time
Abdominal ultrasound for signs of cirrhosis, portal hypertension, and
masses
Surveillance for hepatocellular carcinoma with a-fetoprotein testing
after pregnancy
IgM, immunoglobulin.
hypertension are usually seen after the 4th or 5th decade,
but they have been reporteddalbeit rarelydamong
women of reproductive age. Pregnancies complicated by
detection of cirrhosis and/or portal hypertension are
associated with severe maternal morbidity and mortality.35
Specialist referral needs to be expedited if there are any
signs of chronic liver disease on exam, abnormal ALT,
detectable HBV DNA viral load and cirrhosis, or changes
suggestive of portal hypertension on ultrasound. Transient
elastography, a highly accurate, ultrasound-like, non-inva-
sive imaging technique that maps the elastic properties of
soft tissue and is widely used for the detection cirrhosis, is
currently not recommended for maternal assessment of
CHB complications during pregnancy, as its safety and
performance have not been established in pregnancy.
Obstetric care providers should be aware that women of
African origin exhibit higher rates of HCC than other
CHB-infected women and do so at a younger age.10 Adult
guidelines recommend surveillance for HCC for African
patients starting at age 20 with periodic serum alpha-
fetoprotein determinations and liver ultrasounds. Alpha-
fetoprotein is physiologically elevated during pregnancy,
consequently complete HCC surveillance needs to be de-
ferred to the postpartum period.
TREATMENT OF HBV INFECTION IN PREGNANCY
Indications for antiviral treatment
Antiviral treatment against HBV infection during pregnancy
should be considered for two different reasons: a) for
maternal health and b) for the prevention of perinatal
transmission among those at the greatest risk of PEP failure
due to high HBV DNA viral loads. Treatment indications
apply both to acute and chronic hepatitis B infections.
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Treatment for Maternal Health
Women known to have CHB prior to pregnancy should be
evaluated and treated according to adult guidelines.36,37
Similarly, pregnant women for whom treatment is indi-
cated for their own health should not have treatment
withheld or interrupted during pregnancy.
If a pregnant woman remains untreated during pregnancy or
discontinues HBV treatment during pregnancy or soon after
birth, close monitoring is necessary as there is a risk of
hepatitis ares, especially in the postpartum period.38
Postpartum HBV ares have been observed in up to 25%
of women with CHB,39 and are thought to reect immune
reconstitution. HBV ares appear to be more common in
women who are HBeAg positive,39 and among women
undergoing HBeAg seroconversion. Flares can be asymp-
tomatic and only detected by liver enzyme elevation; up to
50% of women may have mild to severe fatigue, nausea, loss
of appetite, jaundice, and right upper quadrant pain.
Treatment for the Prevention of Perinatal
Transmission
Antiviral therapy with a nucleoside reverse transcriptase
inhibitors, starting between 28 to 32 weeks GA, is rec-
ommended to reduce the risk of HBV perinatal trans-
mission among HBsAg-positive pregnant women with an
HBV DNA level > 200 000 IU/mL (> 106 copies/mL).36
Several studies done in settings where post exposure pro-
phylaxis is routine showed no perinatal transmission where
mothers viral loads were < 106 copies/mL (< 200 000 IU/
mL).21,22,26 The same threshold was found in a meta-
analysis of lamivudine for the prevention of perinatal
transmission.26 Perinatal transmission has been documented
at higher HBV DNA viral load levels (see section above on
perinatal transmission). A recent meta-analysis of 26 studies
that incorporated data from 3622 women, demonstrated a
70% reduction in perinatal transmission (infant HBsAg at 6
to 12 months, relative risk 0.3; 95% CI 0.2 to 0.4 or infant
HBV DNA seropositivity at 6 to 12 months, relative risk
0.3; 95% CI 0.2 to 0.5) with any antiretroviral use (lam-
ivudine, tenofovir, and telbivudine) in the third trimester
among infants who received neonatal PEP.40
Choice of Antiviral Treatment
At the present time, tenofovir represents the most
reasonable choice for treating pregnant women with HBV
infection for either maternal or infant benet, as it is the
most potent nucleoside analogue with the lowest rate of
genotypic resistance,36,37 and available safety data for use
during pregnancy.
Tenofovir is a nucleoside reverse transcriptase inhibitor,
FDA category B drug. The standard dosage of tenofovir is

300 mg po once a day. It is started between 28 and 32
weeks of pregnancy and continued until delivery. To
minimize the possibility of hepatitis ares post-partum,39
continuation of tenofovir until 4 to 12 weeks postpartum
could be considered.
Lamivudine has been studied most often for the pre-
vention of HBV perinatal transmission. It is recognized
now that the use of this drug limits maternal future
treatment options as even short term use promotes
lamivudine-resistant viral variants in at least 20% of
users.41 Telbivudine is a synthetic thymidine nucleoside
analog and is a reverse transcriptase inhibitor, which also
acts to inhibit HBV DNA replication. Telbivudine has
been reported to have better efcacy than lamivudine in
clinical trials and is a FDA category B drug. There is no
high-quality evidence comparing lamivudine, tenofovir,
and telbivudine.
Safety of Antiretrovirals During Pregnancy and
Lactation
The safety prole of lamivudine, tenofovir, and telbivudine
has been reported by the Antiretroviral Pregnancy Regis-
try42 and by MotherRisk. The overall rate of congenital
anomalies with lamivudine and tenofovir is 2.8% (CI 2.5%
to 3.2%) which is similar and not signicantly different
from the baseline population risk.40 Despite the reassuring
safety proles, to date, no treatments have been approved
for the prevention of maternal to child transmission of
hepatitis B by either Health Canada or the United States
FDA.
A recent study among infants born to HIV-infected
mothers reported that whole-body bone mineral content
among tenofovir-exposed infants was 12% lower
compared to un-exposed infants.43 The long-term clinical
signicance of these changes is unknown, as no difference
was seen in growth in prior studies,44 and differences were
not apparent by two years of age.45 Most of these data are
derived from studies of HIV-infected women on tenofovir,
and whether these results are applicable to HBV-infected
women with third-trimester exposures is unknown.
Lactation data for tenofovir are limited, but tenofovirs
pharmacokinetic properties predict close to zero breast-
milk levels. Tenofovir has been detected in breast milk,
but at negligible concentrations (0.03% of the recom-
mended pediatric dose).46,47 Furthermore, infants expo-
sure to tenofovir from breastmilk is lower than exposure
in-utero.48
The safety of entecavir in pregnancy is not known, and
interferon therapy is contraindicated.
Hepatitis B and Pregnancy
Perinatal Precautions and Mode of Delivery
Most cases of perinatal transmission occur when the infant
comes into contact with infected vaginal blood and se-
cretions at the time of delivery, so invasive procedures like
internal fetal monitors, episiotomy, and/or operative
vaginal delivery can theoretically increase the risk of
transmission. Premature rupture of membranes has been
quoted as a risk factor for HBV transmission; however,
data have been inconsistent.20,49 Neonatal PEP should
ameliorate these risks, yet these factors should be consid-
ered during labour of women at the highest risk of peri-
natal transmission (i.e., high HBV DNA viral loads).
Cesarean delivery should not be performed for the sole
indication of preventing perinatal transmission, as benet
has not been found in well-conducted controlled trials.50,51
Breastfeeding
Breastfeeding does not pose an additional risk of HBV
infection, even without neonatal vaccination52,53; hence,
mothers with chronic hepatitis B infection who wish to
breastfeed should be encouraged to do so. Even though
HBV DNA can be detected in breast milk, best available
evidence has not documented an increased risk of vertical
HBV transmission among breastfed infants compared to
bottle-fed infants.52 Mothers with CHB who are breast-
feeding should be advised to exercise care to prevent
bleeding from cracked nipples and to seek medical atten-
tion if they do so.
Women who require continuation of HBV antiviral treat-
ment for their own health and wish to breastfeed should be
supported based on available data and despite controversy
surrounding lactation while on tenofovir (see above).
Continuation of antiviral treatment should also be
considered for women likely to develop postpartum HBV
ares. Specialist (gastroenterology, infectious diseases, or
hepatology) input is needed to determine whether a
woman should continue therapy or not.
OTHER ASPECTS OF MATERNAL CARE
Hepatitis B immunization is acceptable for use in pregnancy.
Pregnant women who are not immune to HBV maybe be
vaccinated, and those who are at risk of HBV infection
should be vaccinated during pregnancy (HBsAg-positive sex
partner, evaluated or treated for a sexually transmitted dis-
ease, recent or current injection drug use, etc.).
Pregnant women with CHB found to be susceptible to
hepatitis A should be offered HAV immunization, because
HAV can follow a severe clinical course in pregnancy and
another viral hepatitis results in compounded morbidity.
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CLINICAL PRACTICE GUIDELINE
Pregnancy also constitutes a window of opportunity for
prevention and education: women with CHB should be
counseled against using hepatotoxic substances including
prescription and over-the-counter medications, herbals,
and alcohol even when not pregnant. They should be also
be counseled regarding risk of transmission to other family
and household members. Sexual partners and household
members should be evaluated for HBV status and referred
for immunization as appropriate.
MATERNAL EXPOSURE TO HBV DURING
PREGNANCY
As with the non-pregnant patient, susceptible patients
exposed to HBV should receive HBIG and start the
hepatitis B vaccine series. Patients who become pregnant
while receiving the vaccine series must be encouraged to
complete the series. Due to common mode of trans-
mission, HIV testing is recommended for all women with
documented hepatitis and all exposures to hepatitis B or C.
NEONATAL PEP
The most effective means to prevent perinatal transmission
is through neonatal PEP. PEP includes HBIG and re-
combinant hepatitis B immunization series starting at birth.
This regimen has been shown to be up to 95% effective in
preventing perinatal transmission of hepatitis B.54
HBIG provides immediate protection through passive
immunity; the dose for newborns is 0.5 mL intramuscu-
larly. The rst immunization should be given within the
rst 12 hours of life; the dose is 0.5 mL intramuscularly
and should be given at the same time as HBIG, but in
different sites.
In Canada, there are several authorized hepatitis B im-
munization schedules, so timing of second and third doses
can differ among provinces. In general, the second and
third vaccine should be given at approximately one month
and six months of life (with at least four weeks between the
rst and second vaccine, two months between the second
and third vaccine, and four months between the rst and
third vaccine).55 Infants born to hepatitis B-positive
women and who are preterm or less than 2000 g require
four doses of vaccine.55
HBsAg and anti-HBs need to be performed on the baby 1
to 4 months after completion of the hepatitis B vaccine
series and at age no younger than 9 to 12 months to
determine if the child developed a protective immune
response to vaccination or if further management for
hepatitis B infection is required.56
8 l - JOGC - 2016
It is essential that we, as obstetric providers, encourage
mothers with CHB to have their infants complete their
HBV immunizations. In a recent cohort from British
Columbia, only 79% received complete PEP, and 24% did
not receive appropriate testing after PEP or were lost to
follow-up.8
PRIMARY PREVENTION IN CANADA
In 1992, the World Health Organization recommended
that all countries include hepatitis B vaccine in their routine
immunization program. Canada has embraced this
recommendation: some provinces immunize during in-
fancy and others in pre-adolescence. However, current
evidence suggests that directing hepatitis B immunization
resources towards universal immunization of infants pro-
vides the best protection at the most relevant age. Delaying
HBV immunization until adolescence misses the critical
time period when risk of acquisition is the greatest (90%
vs. 5%), and the long-term risk of sequelae is higher.57 The
Canadian Paediatric Society has published a position
statement, calling for the harmonization of immunization
schedules in Canada and advocating for universal HBV
immunization during infancy.58 The Society of Obstetri-
cians and Gynaecologists of Canada agree with this posi-
tion statement and echo the call for a harmonized
immunization schedule in Canada.
RELATED WEBSITES AND READING
World Health Organization
Canadian Paediatric Society
Canadian Association for the Study of the Liver Consensus
Guidelines
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