Niger J Paediatr 2016; 43 (3): 201 – 208
Prevention of mother to child
transmission of hepatitis B virus
infection in Nigeria: A call to action
Accepted: 2nd June 2016
women with HBeAg positivity and
hara Africa including Nigeria has
high viral load, infant post-
second largest global burden
exposure prophylaxis and follow-
Department of Paediatrics,
chronic carriers of hepatitis B
of infants of HBsAg positive
College of Medicine, University of
Nigeria, Enugu Campus, Nigeria.
virus (HBV) infection after Asia.
There is no co-ordinated PMTCT
(MTCT) of HBV is the most com-
HBV programme in place in our
mon route of transmission in high
setting despite the huge burden of
Department of Paediatrics,
endemic areas .MTCT of hepatitis
the disease in Nigeria. Hence the
College of Medicine, Ebonyi State
virus infection continues to
need therefore to develop a home
University, Abakaliki/Federal Teaching
occur despite the interventions of
grown PMTCT programme of
Hospital Abakaliki, Nigeria.
hepatitis B vaccinations and im-
HBV to help tackle the burden of
munoglobulins in settings where it
the disease in our country. An evi-
Department of Paediatrics,
practiced. Infants most at risk
dence based review of current best
College of Medicine, Enugu State
are those whose mothers have
practice guidelines for the preven-
University of Science and Technology
high HBV DNA viral loads and
tion of mother-to-child transmis-
(ESUT)/ESUT Teaching Hospital Park
produce the protein HBeAg. Vari-
sion of HBV for use in low and
Lane Enugu, Nigeria.
ous Nigerian studies have re-
medium resource income settings
ported high HBV infection rates
with hepatitis B hyperendemicity
well as HBeAg positivity
will be quiet apt in this circum-
among pregnant women.
These HBV infections usually
This document therefore will be
occur intrapartum and rarely in-
useful as a quick guide to Paedia-
utero. Mothers with HBeAg posi-
tricians, Obstetricians, Family
tivity known to be associated with
Physicians, General Practice Doc-
higher HBV DNA viral loads
tors and other allied health workers
have been linked with higher
charged with the care of pregnant
chances of MTCT as HBeAg is
mothers and their young children.
the only structural HBV protein
that can cross into the placental
lished in English language or
the absence of post exposure
searched manually and electroni-
prophylaxis about 40 percent of
cally in PUBMED and SCOPUS
infants delivered by HBV infected
for the period between 1990 and
mothers could develop HBV in-
2016 on the subject. Keywords
fections, and about 25% of them
searched included: epidemiology
may come down with chronic
HBV infection, MTCT of HBV,
hepatitis and resulting possible
its preventive strategies in-
complications including liver cir-
cluding prenatal screening, anti-
rhosis and hepatocellular cancer
viral agents in pregnancy, infant
later in life.
post exposure prophylaxis and
The prevention of transmission of
follow-up of infected children.
retroviral infection from mother-
to-child has been a success story
HBV epidemiology, MTCT,
the 21 century and such feat
and preventive measures as well as
could be replicated for HBV in-
follow – up models were retrieved
fection. The standard PMTCT of
HBV currently will comprise:
timely prenatal screening, starting
all pregnant women for HBV
anti-viral therapy for pregnant
infection is the most effective
strategy for the prevention of
mothers should receive timely
Key words :
MTCT of HBV, as effective pre-
post exposure prophylaxis and
child transmission; Hepatitis B
ventive measures could be applied
followed up for possible develop-
virus infection; Resource limited
starting from pregnancy to deliv-
ment of chronic hepatitis B infec-
ery while infants of HBsAg posi-
prophylaxis (PEP) using the administration of hepatitis
vaccine within 24 hours of birth followed by comple-
Hepatitis B virus (HBV) infection is a potentially life
tion of the HBV vaccine series; are recognized strategies
threatening liver infection. It is a major global public
for reducing MTCT transmission rates and the global
burden of a new chronic HBV infection.
health problem and known to cause chronic hepatitis
with high risk of mortality resulting from hepatic cirrho-
sis and cancer. Sub-Sahara Africa has the second largest
The World Health Organization has actively initiated
global burden of chronic carriers of HBV infection after
responses to the control of HBV pandemic through pro-
moting the prevention of its transmission.
Asian continent. Estimates of hepatitis B antiginaemia
seroprevalence of 6-20% have been reported, making
Sub-Sahara Africa a hyper-endemic region. Nigeria
note also is that even where women have access to
also is a hyper-endemic country for HBV infection, with
birth dose vaccine of HBV and hepatitis B immu-
varying reported rates ranging from 0.5 to 44.7 percent
noglobulin there remains a 5-10 percent failure rate.
This occurs in women with high HBV viral loads. In this
group of mothers, antiviral therapy during pregnancy
highly endemic regions HBV infection is commonly
has been shown to significantly reduce the risk of
spread from mother to child prenatally, during the pe-
circumstances where mothers do not need
riod of delivery (perinatal transmission), or through
the anti-viral therapy for their own (HBV infection)
horizontal transmission (exposure to infected blood/
health; the antiviral therapy could be used during preg-
body or other fluids) particularly from an infected child
nancy with the aim of reducing the risk of MTCT of
an uninfected child during the first five years of
Nigeria varying reports of horizontal as well as
vertical transmission as the most common route of HBV
Considering that the prevention of transmission of retro-
transmission in children exist.
viral infection from mother-to-child has been a success
story in this 21 Century. Such feat could be replicated
has also been shown to occur during pregnancy
HBV infection particularly in hyperendemic settings
and/or delivery. Mother-to-child transmission (MTCT)
HBV infection has been reported to be responsible for
However gaps still exist on the current recommenda-
over a third of cases of chronic HBV infections world-
tions for managing HBV infected mothers as well as
wide. Hepatitis B infection in pregnancy poses a seri-
their exposed infants particularly in our setting. Also
ous threat to the infant at birth.
failure in follow-up of HBV exposed infants abound
the absence of post exposure prophylaxis, about 40
despite the potential complications associated with
percent of infants delivered by HBV infected mothers
chronic HBV infections particularly liver cirrhosis and
could develop HBV infections, and about 25% of whom
will die resulting from complications of chronic liver
Several Nigerian studies in pregnant women
therefore becomes pertinent to review the literature on
have reported HBV rates between 8.3 to 12.8 per-
the current best practice guidelines on prevention of
mother-to-child transmission (PMTCT) of HBV infec-
tion in other to further empower our clinicians particu-
MTCT of hepatitis B virus infection continues to occur
larly Obstetricians and Paediatricians alike as well as
despite the interventions of hepatitis B vaccinations and
other allied health professionals in addressing this prob-
immunoglobulins in settings where it is practiced. It is
lem adequately in other to reduce the burden of HBV
pertinent to understand that the most significant risk
through vertical transmissions in high endemic settings
factor in transmission of HBV is high maternal viral
Nigeria has introduced the birth dose of hepatitis B vac-
Nigerian studies have shown high levels of HBeAg posi-
cine as well other primary series hepatitis B vaccination
since 2004. The birth dose of HBV vaccine has been
tivity in pregnant women.
Despite presence of hepatitis B surface antigen positiv-
shown to be strategic towards PMTCT of HBV, how-
ity, mothers who are HBeAg with HBV DNA levels
ever ensuring universal HBsAg screening in pregnancy,
greater than or equal to 10 copies per mililitre (greater
starting anti-viral therapy for pregnant women with
than 200,000 in/ml) are at greatest risk of transmitting
HBeAg positivity and high viral load, timely administra-
HBV to their infants.
tion of the birth dose of HBV vaccination and follow-up
exposed infants will remarkably help to realize this
Screening pregnant women for HBsAg (HBV infection),
objective of PMTCT of HBV. Also efforts should be
starting anti-viral therapy for those with HBeAg positiv-
made to educate carrier mothers (after testing) and their
ity and high viral load, providing infant post-exposure
families on the prevalent risk factors and essence of pre-
particularly in third trimester of pregnancy or intrapar-
tum carries the highest risk of transmission of HBV in-
Current implications are that there is urgent need for
Nigeria and other countries in the Sub- Sahara Africa as
well as Asia where hyper-endemicity of HBV exist to
The risk of maternal transmission of HBV infection in
articulate evidence – based, home adaptable and sustain-
and peri-natal period is dependent on mater-
programmes on prevention of mother-to-child-
HBeAg positivity. Mothers with positive HBeAg
transmission of HBV geared towards the eradication of
have a transmission rate of 70-90 percent whereas those
the HBV infection.
with a negative HBeAg have a rate probably less than
Nigeria the current national programme on the
PMTCT of human immune deficiency virus (HIV) in-
However the precise mechanism of HBV transmission
fection could be leveraged upon in the realization of
remains largely uncertain but it appears that infection
HBV prevention. All that is needed is the political will,
may occur intrapartum, or rarely, in-utero.
which basically implies political strategic financial in-
Hepatitis B viral DNA and HBsAg have been detected
vestment in the programmes to make the PMTCT of
amniotic fluid, placental cells and virginal secretions
HBV in Nigeria - a dream come true.
HBsAg positive women during pregnancy and in cord
blood of their neonates.
Hepatitis B Virus Pathology
The HBV is a member of the hepadnaviridae family (a
hepatotropic group of DNA viruses).
The possibility of prenatal transmission of HBV has
The mature HBV virion is a spherical double layered
been speculated to be low.However, mothers with
particle” that has 4 different genes including the
HBeAg positivity known to be associated with higher
outer surface envelop of glycoprotein (hepatitis B sur-
HBV DNA viral loads have been linked with higher
face antigen; HBsAg); an inner portion of the virion
chances of MTCT as HBeAg is the only structural HBV
protein that can cross into the placental circulation.
designated as hepatitis B core antigen (HBcAg), the
nucleocapsid which encodes the viral DNA and a non-
structural antigen known as hepatitis B epsilon (e) anti-
gen (HBeAg). The HBeAg is a non-particulate soluble
antigen from HBeAg by proteolytic self clearage.
The intra-partum period has been shown to be associated
with higher chances of MTCT of HBV.
The HBeAg is a marker of active viral replication and
This exposure occurs via micro-transfusion or haema-
correlates favourably with HBV DNA levels. The HBV
tologic leaks of maternal blood to the fetus during con-
virion also contains a DNA polymerase which exhibits
tractions or through inoculations of mucosal membranes
reverse transcriptase activity and genomic replication
breaks in the skin (e.g. during some obstetric proce-
occurs through an intermediate RNA template as well as
dures including insertion of fetal scalp electrodes in set-
tings where it is practised.
protein from the x-region (HBX) which is needed for the
viral replication and acts as a transcriptional transactiva-
tor of the viral genes and a wide range of host gene pa-
The mode of delivery (vaginal or caesarean section)
does not seem to increase or decrease the risk of perina-
tal HBV infection. Most studies found no difference in
The replication of HBV occurs usually in the liver; how-
MTCT among babies delivered by caesarean or sponta-
ever it could occur in the lymphocytes, spleen, kidneys,
neous versus operative vaginal deliveries among infants
who received post exposure prophylaxis (PEP).
However there is no consensus recommendation as per
Mother-to-child transmission of hepatitis B virus infec-
the preferred mode of delivery in high risk mothers.
Prior to the era of the introduction of universal hepatitis
vaccinations the possible risk of a child becoming a
Though possible markers of HBV have been demon-
chronic carrier of hepatitis B virus infection was
strated in breast milk and colostrum from HBsAg –
women; transmission of HBV through breast
about10 – 30percent if born to mother who is HBsAg
positive but HBeAg negative; and up to 90% if mother
milk is not a significant source of infection, as reported
also HBeAg positive.
some pre- HBV routine neonatal prophylaxis stud-
The most important risk factor for the transmission of
hepatitis B in pregnancy is the maternal HBV DNA lev-
Reported prevalence of HBV infection in breastfed and
els. It has also been proven that failures in MTCT infant
non-breastfed infants appear same, however, some of the
post exposure prophylaxis (PEP) usually occur in moth-
studies did not take maternal HBV DNA viral load into
ers with HBV DNA viral threshold of ≥10 to ≥10 cop-
cognizance. Also, mothers with cracked or bleeding
ies per mililitre. Maternal acquisition of HBV infection
nipples may momentarily stop breastfeeding as meta-
analysis of studies among mothers with absence of such
PMTCT programme as the maternal status is obtained
early enough and appropriate measures applied.
symptoms did not identify an increase in MTCT rates of
when breastfed babies received post exposure pro-
Rapid immunochromatographic hepatitis B surface anti-
gen tests with acceptable performance are available to
is recommended that HBV positive mothers should
identify HBV infected pregnant women.
breastfeed their infants provided that the infants receive
timely and adequate PEP at birth.
Cost-effective point-of-care tests for combined HBsAg
and HBeAg detection and determination of HBV viral
load are currently being developed and further re-
sources should be channeled towards making it a suc-
cases of acute HBV infection usually manifest
non-specific presentations including nausea, vomit-
loss or poor appetite, fever, myalgia and weak-
Prenatal prevention for mothers
The maternal HBeAg positivity as well as elevated HBV
One percent of cases of acute hepatitis including those
DNA viral load are directly related to rate of intrauterine
transmission. Therefore reduction of maternal DNA
occurring in neonatal period may develop fulminant
hepatitis. Course of cases of acute, fulminant hepatitis B
viral load of HBV is an effective method of decreasing
virus infection could be irreversible and result in liver
the rate of HBV infection in infants particularly in en-
failure with possible mortality.
Majority of cases of HBV infections including acute and
Use of anti-viral agents in pregnancy
chronic hepatitis are asymptomatic. Chronic HBV infec-
tion however has three immunologic phases: immune
The probable reasons for use of anti- viral (anti-
tolerant (absent or minimal liver inflammation, high
retroviral) therapy in chronic hepatitis B in pregnancy
viraemia); immune active (alanine amino-transferase
are based on maternal viral load, liver enzyme levels
rises, high viraemia, liver inflammation rises; high vi-
(liver function test), HBeAg status, liver histology, and
HIV co-infection status.
raemia, liver inflammation, and fibrosis improve, anti-
HBe is present); and the inactive chronic hepatitis (the
non-replicative or inactive immune-control phase) which
The benefits of anti- retroviral (ARV) prophylaxis dur-
follows successful sero-conversion from an HBeAg –
pregnancy is to decrease viraemia so as to limit
breakthrough HBV infection. The administration of
positive to anti-HBe state.
The immune tolerant phase usually appears in individu-
anti- retroviral therapy (ART) starting from late preg-
als who had perinatal infection from HBeAg positive
nancy will reduce maternal HBV viral load and poten-
tially reduce the possible risk of MTCT.
The use of antiviral agents during pregnancy mainly for
prophylaxis of perinatal HBV transmission would entail
Prenatal hepatitis b virus infection screening
diligent evaluation of potential risks and benefits among
infants and their pregnant mothers alike. Some studies
Chronic HBV infection is characterized by the presence
animal specimens have shown severe growth restric-
HBsAg for at least 6 months (with or without concur-
tion and reduced bone mineral density in exposed fe-
rent HBeAg positivity). The persistence of HBsAg is the
tuses to ART.
principal marker of risk of developing chronic liver dis-
ease and hepatocellular carcinoma later in life.
However, recent efficacy data on prophylaxis of
PMTCT of HBV have shown acceptable safety profile
is recommended that all pregnant women should be
pregnant women. Equally commencement of the ART
tested routinely for HBsAg during an early prenatal visit
the third trimester of pregnancy among mothers with
(preferably in the first trimester) in every pregnancy
high viral load (e.g. ≥10iU/mL) to prevent breakthrough
irrespective of if they had been previously vaccinated
perinatal HBV transmission has also been successful
for HBV or tested.
without concerns. Tenofovir, lamivudine and telbi-
Un-booked pregnant mothers or women who were not
vudine are nucleos(t)ide inhibitors which act as chain
screened prenatally particularly those who engage in
termination in DNA elongation and can be administered
from 28 weeks of pregnancy.
behaviours that put them at high risk for infection espe-
cially intravenous drug users, those with more than one
sexual partners in the previous six months or an HBsAg-
Initially lamivudine (3TC) was commonly used with
positive sex partner, evaluation or treatment for a sexu-
benefit of reduction in transmission of HBV transmis-
ally transmitted disease and those with clinical hepatitis
sion; however, it was shown to be associated with devel-
should be tested at the time of admission to the hospital
opment of resistance owing to its low genetic barrier. On
other hand, tenofovir, has a high barrier to resistance
has been used extensively in the setting of HIV in
prenatal HBsAg screening is key to successful HBV
pregnancy. Use of tenofovir in pregnancy has resulted in
significant reductions among mothers, without any re-
serves as a safety net as non-testing, errors in testing,
markable adverse effects.
reporting and documentation of maternal HBsAg status
Based on safety data from the ARV in Pregnancy Regis-
in pregnant HIV positive women who have received
the United States, the CDC in 2005 recommended
tenofovir and/or lamivudine or emtricitabine; tenofovir
that the Advisory Committee on Immunization Practices
appears to be the preferred ARV, owing to its better
(ACIP) and all health professionals should administer
resistance profile, and more extensive safety data in
the HBV vaccine to all newborns before hospital dis-
pregnant HBV positive mothers.
charge in order to protect them against the HBV ifneci-
ongoing caution is being advised on the use of ART
pregnancy; the absence of adverse drug events in
However, in Nigeria it has been noted that many babies
mothers and their infant pairs who received ART in
were delivered in health facilities do not receive
pregnancy up to date offers promise in their use. Some
birth dose of recommended vaccinations before the
hospital discharge. Nigeria recommends that the birth
guidelines recommend treatment for non-cirrhotic pa-
tients (including pregnant woman) with serum HBV
of HBV should be given preferably within the first
DNA levels greater than 20,000 iu/mL (> 10 copies/
24hours of birth but up to first 2 weeks of life. This birth
mL) and evidence of liver disaes.
dose is usually given as a monovalent vaccine. It is of
note that giving the birth dose after the neonatal period
reduces the efficacy of PEP which decreases with in-
creasing time as exposure.
of monitors should be avoided as much as possible.
centres where it is obtainable the use of fetal scalp
Nigerian HBV Vaccination Schedule
electrode monitoring as well as fetal blood sampling
should be avoided particularly if mother is HBeAg posi-
birth dose of HBV vaccine followed by two more
tive. Also standard precautions should be implemented
doses to complete the primary series is the conventional.
care of all women in labour. Appropriate cleaning of
However, WHO recommends that four doses may be
newborn should equally be practiced- upon delivery
given in line with the programmatic protocol of National
neonate’s eyes as well as the non - intact skin should
cleaned properly using water as soon as possible after
The pentavalent vaccine which replaced the trivalent
DPT was introduced in Nigeria in 2012, and contains
HBV vaccine among others as a combination vaccine to
commenced at age 6 weeks through ten and 14 weeks
The double usage of active and passive immuneprophy-
respectively. However, Nigeria currently gives the birth
laxis is the ideal measure to prevent MTCT of HBV
dose in addition to three combined doses in form of pen-
tavalent vaccine doses.
PEP with hepatitis B vaccine and hepatitis B immune-
globulin (HBIG) administered within 12 to 24 hours
The complete vaccine series induces protective antibody
after birth followed by completion of a three dose vacci-
levels in more than 95% of infants, children and young
nation series, has been shown to protect 85 to 95% of
adults. Protection lasts at least 20 years and is probably
life long. The vaccine has excellent record of safety and
infants whose mothers were positive for both HBsAg
effectiveness and the immunogenicity of the combined
hepatitis vaccines is equivalent to that of their individual
Birth dose hepatitis B vaccine
antigens administered separately.
The recombinant DNA – derived hepatitis B vaccines
Immunization escape mutants in the S – gene of HBV
have been available and licensed for use since 1982. The
have been detected, and concerns have been expressed
World Health Organization (WHO) as well as the Cen-
that these variants could replicate in the presence of vac-
ters for Disease Control (CDC) recommends universal
cine induced anti-HBS or anti-HBS contained in HBIG.
HBV vaccination for all infants, and that the first dose
However no evidence exist that s-gene immunization
should be given as soon as possible after birth preferably
escape mutants posing a risk to currently existing pro-
grammes using hepatitis B vaccine.
within the first 12 hours of birth.
Further studies including surveillance are needed to
Nigeria the universal HBV vaccination was initiated
track any possible emergence of these variants in future.
the Federal Government in 2004; despite that huge
gap still exists in meeting the targets as majority of the
Vaccinations in preterm/Low Birth Weights
children receive the birth dose vaccine outside the rec-
ommended time owing to maternal as well as pro-
Previously, the American Academy of Pediatrics (AAP)
gramme – related factors.
routinely recommended that the birth dose of HBV vac-
cine for preterm and low birth weight infants born to
The birth dose of HBV vaccine is very important as that
HBsAg negative mothers be delayed up till the infant
weighed 2 kilograms or is two months of chronological
Follow – up
age, owing to reduced immunogenicity in preterm less
than two kilograms (<2kg). However recent guidelines
MTCT of hepatitis B virus continues to occur despite
the AAP recommends that such children should re-
the use of adequate preventive measures including vac-
cinations and HBIG administration. The ACIP recom-
ceive the first dose of hepatitis B vaccine by 30 days of
chronological age irrespective of the gestation age. Also
mends post-HBV vaccination testing for all infants born
such preterm/LBW shows consistent weight gain ne-
HBsAg positive women. The testing consists of
cessitating hospital discharge before 30 days of age, the
HBsAg for infection and anti-HBS for response to vac-
first dose of hepatitis B vaccine should be given at the
cination. The optimal timing for detecting protective
time of hospital discharge. The remaining three doses of
antibodies is one to 2 months after the final Hepatitis B
hepatitis B vaccine series should be completed on the
vaccine dose at ≥ 9 months of age. The testing for fol-
same schedule as applicable to full term infants, ensur-
low-up should commence at 9 to 18months of age, at
least 1month after the last dose of vaccine.
that the second dose is given at least 30 days after
the initial dose.
The anti-HBS levels done earlier than 9 months of age
may reflect passive immunization with HBIG.
Also of note is that currently the ACIP does not recom-
routine booster doses of hepatitis B vaccine for
HBS levels of more than 10m/u/L indicate adequate
persons who completed the primary HBV immunization
protection whereas babies with anti-HBs levels of less
series in childhood.
than 10m/u/L need to be re-vaccinated with the entire 3
The immunogenicity of hepatitis B vaccine is low in
individuals with severe immunosuppressive states in-
Babies who are HBsAg positive are infected and need
cluding AIDS, and timely administration of the HBV
further evaluation and follow-up by a paediatric gastro-
vaccine commencing at birth should be the rule rather
than the exception as the HIV immunosuppression wors-
ens overtime among infected children.
Currently Nigerian Society for Paediatric Gastroenterol-
Hepatitis B vaccination is recommended in HBsAg
ogy Hepatology and Nutrition (NISPGHAN) and Soci-
negative women in pregnancy with high likelihood of
ety for Gastroenterology and Hepatology in Nigeria
acquisition of the infection particularly in those having
(SOGHIN) are in the forefront of spreading the good
multiple sexual partners or intravenous drug abusers.
news of HBV prevention in Nigeria and should be en-
couraged by the authorities by doing the needful.
provides passively acquired anti-HBS and temporary
protection when administered in standard doses. Hepati-
tis B immuneglobulin (HBIG) is typically used as an
Universal screening of all pregnant women for HBV
adjuvant to the hepatitis B vaccine in the PMTCT of
infection is the most effective strategy for the prevention
hepatitis B infection in exposed infants, providing tem-
MTCT of HBV, as effective preventive measures
porarily protection for 3 to 6 months.
could be applied starting from pregnancy to delivery
while infants of HBsAg positive mothers should receive
Administration of hepatitis B immuneglobulin and hepa-
timely and adequate PEP as well as follow up for possi-
titis B vaccine within 24 hours of birth, followed by the
ble development of chronic hepatitis B infection.
completion of the vaccine series is 85 – 95% efficacious
PMTCT of HBV.
HIBG administered alone is the primary means of pro-
CBE: Study conceptualization, literature search,
tection after an HBV exposure for non-responders to
manuscript draft, critical editing of the manuscript for
hepatitis B vaccination.
important intellectual content.
NBO, OFA: Critical editing of the manuscript for im-
portant intellectual content.
Conflict of Interests: None
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