The prevention of transmission of retroviral
infection from mother to child has been a success story of our times and
indeed, PMTCT is now synonymous with prevention of HIV infection.
However, awareness of the current recommendations for managing babies of
mothers who are hepatitis B carriers is not universal, resulting in
failure of follow up, despite the serious long term implications
including development of hepatic carcinoma. A review of current
guidelines would help in empowering pediatricians to address this
problem effectively, and ensure that vertical transmission of hepatitis
B infection is prevented. Although the introduction of the birth dose of
hepatitis B vaccine will go a long way to achieve this objective, there
needs to be a system in place to ensure universal screening during
pregnancy, timely administration of the birth dose and tracking of
babies exposed to hepatitis B. Carrier mothers and their families need
to be educated regarding the risks involved and the importance of
preventive strategies.
Background
It is estimated that 5% of the world’s population is
chronically infected with hepatitis B [1,2]. With a prevalence rate for
HBsAg seropositivity 2-7 %, India has an intermediate endemicity, and a
projected burden of 50 million carriers, the second largest in the world
[3,4].
In India, the HBsAg prevalence rate among pregnant
women varies between 0.9% and 11.2% [5-7]. Hepatitis B e-antigen (HBeAg)
status, which indicates high replicative activity of the virus in the
liver, was less than 30% in most earlier studies on pregnant women,
though a recent study revealed HBeAg seropositivity of 56.8% [6].
Transmission
Without immune prophylaxis, in mothers who are both
HBsAg and HBeAg positive, the risk for transmission to the baby is
between 70 and 90% by 6 months of age, whereas in the case of mothers
who are HBsAg positive, but HBeAg negative, it is less than 10% [8-11].
The increased risk of transmission with HBeAg positive status is due to
high titres of HBV in these women [8]. One study found that 38% of
babies born to HBsAg positive mothers, who did not acquire infection
perinatally, became infected by four years of age [12]. This emphasizes
the need to equip mothers with knowledge to prevent horizontal
transmission of hepatitis B infection, and the importance of completion
of the hepatitis B vaccination schedule.
Implications
The risk for development of chronic hepatitis B
infection varies inversely with the age at which infection occurs, 90%
of affected infants develop chronic infection as opposed to 30-50% of
under-five children and 6% of children above five years of age [13,14].
Chronic hepatitis B infection acquired in childhood carries a 25% risk
for development of chronic liver disease, cirrhosis or hepatocellular
carcinoma [15]. Hence, it is imperative to prevent mother to child
transmission.
Preventive Strategies
Immunoprophylaxis
A combination of active and passive immune
prophylaxis is the optimum strategy to prevent HBV infection in babies
of HBsAg positive mothers. A combination of hepatitis B immune globulin
(HBIG) and hepatitis B vaccination initiated within 24 hours of delivery
has been shown to protect 85 to 95% of babies whose mothers were
positive for both HBsAg and HBeAg [16]. However, studies have shown
significant gaps in hospital practices and policies to prevent vertical
transmission of hepatitis B [17].
Hepatitis B vaccination is carried out using the
monovalent vaccine for the birth dose. Further doses may be administered
as a combination vaccine with other infant vaccines like DPT, DTaP and
Hib vaccines since interference with the immunogenicity of these
vaccines does not occur [2]. Hepatitis B vaccination in infancy had been
adopted by 179 countries by the end of 2009 [18].
Birth dose of hepatitis B vaccine
Administration of single antigen hepatitis B vaccine
soon after birth is critically important for the prevention of perinatal
and early postnatal transmission of HBV infection, and is much more
efficacious for this purpose than doses given after the neonatal period,
since the efficacy of post exposure prophylaxis diminishes with
increasing time since exposure [18].
The birth dose is recommended for all newborns since
it serves as a safety net, due to the fact that errors in testing,
reporting and documenting maternal HBsAg status do occur [19]. Moreover,
the chance for completing the hepatitis B vaccine schedule and in fact
all other immunizations, is found to improve when vaccination is
initiated at birth [20].
The proportion of newborns receiving the birth dose
within 24 hours has been suggested as a useful performance indicator for
immunization programmes by WHO, and coordination between maternal and
neonatal services is of paramount importance to achieve success in this
key task [18].The CDC; however, recommends that the birth dose be given
within 12 hours after delivery [2].
Vaccination schedule
Although the conventional schedule for hepatitis B
vaccination consists of three doses including the birth dose, WHO
stipulates that four doses may be given in concordance with programmatic
requirements of National Schedules [18]. This is of enormous benefit in
reducing the number of clinic visits as well as ensuring compliance, and
is especially important in developing countries with resource
constraints. A combination of HBIG and hepatitis B vaccination initiated
within 24 hours of delivery, followed by a three dose immunization
schedule initiated at 1-2 months of age, has been shown to protect 85 to
95% of babies whose mothers were positive for both HBsAg and HBeAg [16].
The widely spaced schedule with the third dose of
hepatitis B vaccine administered at least 6 months after birth, is
recommended by the CDC for vaccination of babies of HBsAg positive
mothers (2), since the last dose mainly acts as a booster, and is
responsible for providing long term protection. However, WHO differs on
this point, and recommends the closely spaced schedule, asserting that
longer dose intervals may increase the final anti-HBs titres, but not
the seroconversion rates [1].
Special situations
In mothers with an unknown HBsAg positivity status at
delivery, the birth dose of hepatitis B vaccine is administered within
24 hours of birth, and HBIG is administered as soon as possible if the
mother tests positive, ideally within 72 hours of delivery [2,18].
In the case of preterm babies of HBsAg positive
mothers, the birth dose is indicated even if the baby weighs less than 2
kilograms, but should be followed by a further three doses starting at
six weeks of age [21,22]. This is due to the reduced immunogenicity of
hepatitis B vaccine in preterms weighing <2 kilograms in the first month
of life [23].
The immunogenicity of hepatitis B vaccine is
suboptimal in conditions associated with immuno-suppression, including
advanced HIV infection, and is influenced by the viral load, CD4 count,
age, duration of HAART and the presence of AIDS defining conditions
[18]. Hence, early administration of the hepatitis B vaccine starting at
birth is imperative, since immunosuppression increases over time [18].
Interruption of the vaccine series does not warrant
revaccination, but rather completion of the missed dose as early as
possible with a minimum interval of four weeks between two doses [24].
Women who are HBsAg negative in pregnancy, but who
are at high risk of acquiring hepatitis B infection, including those
with a history of multiple sexual partners or of drug abuse, should
receive hepatitis B vaccine [24].
Passive immunization
HBIG is used as an adjunct to the hepatitis B vaccine
to prevent vertical transmission. It provides temporary protection that
lasts for 3 to 6 months. A combination of HBIG with HBV is more
effective than HBV alone in prevention of transmission of hepatitis B
[26]. Studies have shown that HBIG is effective when administered as
late as 72 hours after birth [2].
Administration of a 3 or 4 dose series of hepatitis B
vaccine starting within 12 hours after birth without passive
immunization with HBIG has shown to have a protective efficacy of 70 to
95 % in mothers who were both HBsAg and HBeAg positive [27-30]. The
addition of HBIG to active immunization is particularly beneficial when
the mother is both HBsAg and HBeAg positive. Some studies have shown
that when HBIG is unavailable, vaccination alone can prevent vertical
transmission in 66% to 90% of cases [31]. Moreover, in full-term
newborns, the protection against perinatally acquired infection achieved
by immediate (<24 hours) hepatitis B vaccination is not significantly
improved by the addition of HBIG [1]. This is highly pertinent in
settings like ours where financial constraints often preclude the use of
HBIG.
Breastfeeding
Breastfeeding by an HBsAg positive mother does not
increase the risk of transmission to the baby, and is therefore not
contraindicated , provided the baby is given immunoprophylaxis [32].
Follow up
Although routine post-vaccination testing is not
necessary, it is recommended for high-risk groups including babies born
to mothers who are HBsAg positive, and should commence at 9 to 18 months
of age, atleast 1 month after the last dose of vaccine [18]. HBsAg
status and the anti HBs titre should be checked. The anti HBs levels
done earlier than 9 months of age may reflect passive immunization with
HBIG [2]. Anti HBs levels of more than 10 mIU/l indicate adequate
protection, whereas babies with anti HBs levels of less than 10 mIU/l
need to be revaccinated with the entire 3 dose schedule. Babies who are
HBsAg positive are infected and need to be followed up. Anti HBc testing
is not advised since it may remain positive upto 2 years of age in
babies of infected mothers [2].
More than 95% of healthy newborns respond to a 3 dose
vaccine series, while almost all respond to revaccination [33]. However,
there is no data to suggest any benefit in revaccinating a baby who has
no detectable antibody after 6 doses of vaccine.
Conclusions
The importance of public awareness and education of
medical professionals is well recognized [34]. Education about the
importance of administering the birth dose within 24 hours of birth is
vital [35]. Universal screening of all pregnant women for hepatitis B is
thus a pre requisite for effective preventive services and follow up
care to be put in place.
Newer heat and freeze resistant vaccines are under
development, raising hopes of vaccination on site in the case of home
deliveries [33]. Evidence is emerging to suggest that the antiretroviral
drugs, lamivudine and telbivudine may further prevent vertical
transmission when administered to women with a high HBV viral load in
the third trimester, and a beneficial effect with maternal HBIG has also
been shown to occur [36-39]. Research is being carried out to develop a
vaccine suitable for non- responders to the currently available vaccine.
In conclusion, the differences in the recommendations
of the WHO and CDC are a reflection of the diverse population groups
they represent, the high- prevalence countries with the added burden of
resource and logistical constraints on the one hand, and the low-
prevalence, resource- rich nations on the other.
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