DOI: 10.1111/tog.

12225

2015;17:25763

Review

The Obstetrician & Gynaecologist

http://onlinetog.org

Vaccination in pregnancy
P S Arunakumari

MBBS MD FRCOG MFFP,

a,

* Sujatha Kalburgi

b
MBBS,

Amita Sahare

MD MRCOG

Consultant Obstetrician and Gynaecologist, Basildon and Thurrock University Hospitals NHS Foundation Trust, Nethermayne, Basildon SS16
5NL, UK
b
Specialty Trainee in Obstetrics and Gynaecology, Basildon and Thurrock University Hospitals NHS Foundation, Nethermayne, Basildon SS16
5NL, UK
*Correspondence: P S Arunakumari. Email: ps.arunakumari@btuh.nhs.uk

Accepted on 11 May 2015

Key content


Live attenuated viral and bacterial vaccines are generally

contraindicated during pregnancy because of the theoretical risks
to the fetus.
 No evidence exists of fetal risks from vaccinating pregnant women
with inactivated virus or bacterial vaccines or toxoids.
 Inactivated, recombinant, subunit, polysaccharide, conjugate
vaccines and toxoids pose no risk for breastfeeding mothers or
their infants.
Learning objectives


To provide an overview of the principles of vaccination

in pregnancy.

To improve confidence of healthcare professionals in discussing

aspects of vaccination in pregnancy.
 To provide a quick reference guide regarding the indications,
contraindications and safety of vaccines in pregnancy.
Ethical issues


Is the use of a mother as a vehicle to protect her fetus

ethically justified?
 Is compulsory vaccination of healthcare professionals
ethically debatable?
Keywords: attenuation / lactation / pregnancy / toxoid / vaccine

Please cite this paper as: Arunakumari PS, Kalburgi S, Sahare A. Vaccination in pregnancy. The Obstetrician & Gynaecologist 2015;17:25763.

Introduction
One of the greatest triumphs of immunology has been the
development of vaccines against certain infectious agents.1
Vaccination is one of the most successful and cost-effective
public health interventions; it has led to the eradication of
some diseases (smallpox) and the control of many others
(polio and whooping cough).2
Maternal vaccination protects both the mother and fetus
from the morbidity of certain vaccine-preventable diseases.

Principles of immunology
The human host is endowed with defence mechanisms to
protect the body against foreign environmental agents.

Types of defence mechanisms

The host defence mechanisms can be innate or adaptive.3
Innate, also called natural or native, immunity refers to
those elements of the immune system that an individual is
born with.2 Adaptive or acquired immunity is when the host
adapts to the presence of microbial invaders. The salient
features of these types of immune responses are presented
in Table 1.

2015 Royal College of Obstetricians and Gynaecologists

Induction of immunity
Immunity is defined as resistance to disease, specifically
infectious disease. Immunity may be induced in an individual
by infection or immunisation. Active immunisation involves
the administration of an antigen to stimulate production of
antibodies. Passive immunity involves the administration of
an antibody to confer short-term immunity.

Passive immunity
Passive immunity is useful for rapidly conferring immunity
even before the individual is able to mount an active
response but it does not induce long-lived resistance to
infection.3 The only physiological example of passive
immunity is seen in the neonatal period, where despite
immaturity of the immune system the neonate is protected
against infection by passively transferred antibodies from the
mother through the placenta and the breast milk. Placentallyderived antibodies are of the type IgG. The major
immunoglobulin in milk is IgA. This is not absorbed by
the baby but remains in the intestine to protect the mucosal
surfaces; this maternal antibody attenuates many infections,
allowing neonatal cellular immunity to mature under
controlled conditions.4

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Vaccination in pregnancy

Table 1. Features of the two different types of immunity

Innate immunity

Adaptive immunity

Phylogenetically older
Less specialised
Less powerful
First line of defence
Poor specicity, antigen nonspecic
Rapid response, usually within minutes
Does not react against the host
No memory
Components include epithelial barriers, phagocytes - neutrophils,
monocytes and macrophages

Evolved later
More specialised
More powerful
Subsequent line of defence
High specicity, antigen specic
Slow response, takes days
Can react against the host
Memory evident
Components include lymphocytes (T and B cells)
and their products: antibodies and cytokines

Immunology of pregnancy
During normal pregnancy, the maternal immune system
adapts to accommodate the semi-allogenic fetal graft. This is
essential for the acceptance of the fetus and the development
of the placenta without compromising the integrity of the
maternal host. Nevertheless, this modulation of the maternal
immune system is generally not believed to cause a substantial
difference in the immune response to vaccination.5

Vaccination
Vaccination is the process of stimulating a protective
adaptive immune response against microbes by exposure to
nonpathogenic forms or components of the microbes.3
A vaccine is a biological preparation that improves
immunity to a particular disease. Most vaccines generate
antibodies that prevent the damage caused by toxins or that
neutralise the pathogen. Vaccines work by inducing active
immunity and by providing immunological memory.
Immunological memory allows the immune system to
recognise and respond rapidly to natural infection when
exposed at a later stage; this prevents or modifies the effect of
the disease.6

Types of vaccines
Vaccines can be broadly divided into live vaccines, killed
vaccines and purified macromolecules derived from
pathogens (Figure 1, Table 2).

Live vaccines
Attenuated vaccines utilise microbes that have been treated to
abolish their infectivity and pathogenicity yet still retain
their antigenicity.
With live viral vaccines there is a possibility that the viral
nucleic acid may be incorporated into the host genome or
that there might be a reversion to a virulent form. Further,
live vaccines have the potential to infect the fetus. For these
reasons, use of live vaccines is generally contraindicated

258

during pregnancy. However, these risks must be balanced

against the expected chance of contracting the disease with its
own complications. The riskbenefit ratio of administering
live vaccines to pregnant women should be weighed
individually for each patient in consultation with an
infectious disease expert.

Killed vaccines
Often the immunity conferred by inactivated vaccines is
inferior to that resulting from live vaccines. This is because
the replication of the living microbes confronts the host with
a larger and more sustained dose of antigen. Furthermore, as
these preparations are often injected, the immune response
does not take place at the site of natural infection.

Purified macromolecules
Three general forms of purified macromolecule vaccines are
in current use:
 inactivated toxins
 conjugate vaccines
 subunit vaccines.
Bacterial toxins can be detoxified by formaldehyde
treatment and used to stimulate immunity. Examples
include diphtheria toxoid and tetanus toxoid.
Conjugate vaccines or carbohydrate vaccines are
polysaccharides. As the glycans tend to be poorly
immunogenic, they are conjugated to a carrier protein to
increase their immunogenicity. Examples include
Haemophilus influenzae vaccine, Neisseria meningitidis
vaccine and Streptococcus pneumoniae vaccine.
Subunit vaccines include only the antigens that stimulate
the immune system, for example Dane particle from the
surface antigen of hepatitis B virus (hepatitis B vaccine).

General principles of vaccination

in pregnancy
Ideally women should be vaccinated against preventable
diseases in their environment before pregnancy. When

2015 Royal College of Obstetricians and Gynaecologists

Arunakumari et al.

Killed vaccine

Live attenuated
vaccine

Dead
pathogen

Attenuated
pathogen

Inactivation

Attenuation

Pathogen

Cloning

Fractionation

DNA vaccine

Subunit vaccine

Figure 1. Current vaccine approaches.

Table 2. Differences between live and killed vaccines

Live vaccines

Killed vaccines

Generally require only a single

booster
Less stable
Humoral and cell mediated immunity
induced
May revert to the virulent form
Only small dose required
Given by natural route
More potent

Require multiple boosters

More stable
Mainly humoral immunity
induced
Cannot revert to virulent form
Large dose required
Given by injection (unnatural
route)
Less potent

trimester to allow for completion of the critical period of

fetal organogenesis.7

UK immunisation schedule in pregnancy

immunisation is performed during pregnancy the benefits to

the mother and the fetus should outweigh the risks.
Toxoids, inactivated virus vaccines and immune globulin
preparations
are
generally
considered
safe
for
administration to pregnant women because there is
neither evidence nor biological plausibility of harmful
effects on the fetus or pregnancy. Nevertheless, if prompt
administration is not medically indicated, it is preferable to
delay administration of these agents until the second

2015 Royal College of Obstetricians and Gynaecologists

A temporary programme for the vaccination of pregnant

women against Bordetella pertussis was introduced in October
2012. The purpose of the programme is to boost antibodies
in these women so that they are passed from mother to baby.
This should protect the infant against B. pertussis infection
from birth until they are vaccinated at 2 months of age.
Pregnant women should be offered the diphtheria, tetanus,
pertussis (whooping cough) and polio (dTaP/IPV) vaccine in
weeks 2838 of their pregnancy (ideally in weeks 2832), for
each pregnancy. The pertussis vaccine can be given at the
same time as the influenza vaccine but pertussis vaccination
should not be given early in order to offer the vaccines at the
same time as this will compromise the passive protection to
the infant.
Influenza vaccination during pregnancy will provide
passive immunity against influenza to infants in the first
few months of life following birth. Protection of the mother
should also reduce the risk of her transmitting infection to a
newborn baby. The inactivated influenza vaccine should
therefore be offered to pregnant women at any stage of

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Vaccination in pregnancy

pregnancy (first, second or third trimesters), ideally before

influenza viruses start to circulate. Influenza vaccination is
usually carried out between October and January, however
clinical judgement should be used to assess whether a
pregnant woman should be vaccinated after this period,
taking into account factors including the level and severity of
influenza-like illness in the community and the availability of
inactivated influenza vaccine. The influenza vaccine can be
given at the same time as the pertussis vaccine but the
influenza vaccination should not be delayed in order to offer
the vaccines at the same time.8

Clinical classication of vaccines

In the clinical context, vaccines can be broadly classified
as those contraindicated in pregnancy, those specially
indicated in pregnancy and those generally safe in
pregnancy (Box 1).9

Use of specic vaccines in pregnancy

Bacillus CalmetteGuerin (BCG)
Although no harmful effects of the Bacillus CalmetteGuerin
(BCG) vaccination on the fetus have been observed, BCG
vaccination should not be given during pregnancy due to
theoretical concerns associated with a live vaccine.10

Measles, mumps and rubella

The measles, mumps and rubella (MMR) vaccine and its
component vaccines should not be administered to women
Box 1. Clinical classications of vaccines.
Vaccines contraindicated in pregnancy








BCG vaccine
Measles vaccine
Mumps vaccine
Rubella vaccine
Varicella vaccine
Vaccinia vaccine
Human papillomavirus vaccine

Vaccines specially indicated in pregnancy







Inactivated inuenza vaccine

Pertussis (whooping cough) vaccine
Inactivated polio vaccine
Diphtheria toxoid
Tetanus toxoid

Vaccines recommended in pregnancy in certain situations









Hepatitis A vaccine
Hepatitis B vaccine
Meningococcus vaccine
Pneumococcal vaccine
Rabies vaccine
Typhoid vaccine
Yellow fever vaccine

260

known to be pregnant because of the possible risk of

teratogenic effects of the vaccine on the fetus.11 Women
should be counselled to avoid becoming pregnant for 28
days after vaccination with MMR. However, the UK
Department of Health does not recommend termination
should the MMR vaccine be inadvertently given to a
pregnant woman as studies have failed to demonstrate a
link between rubella immunisation in early pregnancy and
fetal damage.12

Rubella
Where the woman is known to be rubella-susceptible, the
vaccine should be given in the postpartum period.11 A single
dose of the MMR vaccine will suffice. Vaccinated women are
then advised to avoid conception for 28 days after
administration. The vaccine can also be given safely to
postpartum women who are breastfeeding. Although the
rubella virus is excreted in breast milk, only seroconversion
without serious infection has been reported in breastfeeding
infants.11 The children of pregnant women can be vaccinated
without risk to the mother or the fetus since the infection is
not transmitted from recently immunised individuals.

Varicella
Pregnant women should not be vaccinated against Varicella
zoster (chicken pox) because of the known adverse effects of
the varicella virus on the fetus.7,13 Where nonpregnant
women are vaccinated they should be advised to avoid
becoming pregnant for 4 weeks after completing the two dose
vaccine schedule.

Human papillomavirus
Human papillomavirus type 6, 11, 16, 18 virus-like particles
are not recommended for use during pregnancy as their
safety has not been evaluated in pregnant women.14,15 If a
woman is found to be pregnant after initiating the
vaccination series, the remainder of the three dose regimen
should be delayed until completion of the pregnancy.10

Influenza
Influenza is associated with greater morbidity in pregnant
women. Women in the second and third trimester of
pregnancy are at increased risk of hospitalisation from
influenza. Vaccination reduces the risk of serious maternal
medical complications and provides passive protection to the
neonate.16 It is recommended that all pregnant women have
the influenza vaccine whatever stage of pregnancy they are
at.17 However, do not administer the live attenuated
influenza virus vaccine to pregnant women.18

Pertussis (whooping cough)

In September 2012 the Joint Committee of Vaccination and
Immunisation introduced the temporary maternal pertussis

2015 Royal College of Obstetricians and Gynaecologists

Arunakumari et al.

vaccination programme in the UK.19 The purpose of the

programme is to passively protect the infant in the first few
months of life, before they reach the age of routine infant
vaccination at about 8 weeks.20 This is achieved by
vaccinating pregnant women between 28 and 38 weeks of
gestation, in order to maximise the trans-placental transfer of
pertussis antibodies.21

Diphteria, Tetanus, Poliomyelitis

In the UK, Repevax (diphtheria, tetanus, acellular pertussis/
inactivated polio vaccine [DTap]) was the recommended
vaccine for this programme. Although the optimal timing
for the DTaP vaccine administration is between 28 weeks
and 38 weeks of gestation, this can be given at any time
during the pregnancy. In July 2014 Repevax was replaced by
Boostrix IPV the 4 in 1 vaccine containing diphtheria
toxoid, tetanus toxoid, acellular pertussis and inactivated
polio vaccine.8

Hepatitis A
Formalin inactivated Hepatitis A is recommended if another
high risk condition or indication is present.22 High-risk
factors for Hepatitis A23 include:






long-term liver disease

haemophilia
intravenous illegal drugs
working with or near sewage
working in institutions where levels of personal hygiene
may be poor
 working with primates (monkeys, apes, chimps
and gorillas).24

Hepatitis B
Hepatitis B infection in pregnancy may result in severe
hepatic disease for the mother and chronic infection for the
baby. Hence, if a pregnant woman is in a high-risk category,
Hepatitis B vaccination should not be withheld.25 As this is
an inactivated subunit vaccine, the risks to the unborn baby
are negligible.26
Women considered to be at risk of Hepatitis B27 and
would therefore benefit from vaccination28 are:
 women who inject drugs or have a partner who
injects drugs
 women with multiple sexual partners
 women who are close family and sexual partners of a
patient with Hepatitis B
 women who receive regular blood transfusions or
blood products
 women with liver disease or chronic kidney disease
 women travelling to high risk countries
 female sex workers

2015 Royal College of Obstetricians and Gynaecologists

 women who work in settings that place them at risk of

contact with body fluids, such as nurses, doctors, dentists
and lab staff.

Meningococcal vaccine
There is no evidence that either vaccine, the conjugated
the quadrivalent vaccine, is unsafe.29 The usual advice is
avoid vaccination unless the mother is at high risk
disease.30 Women considered to be at high risk
meningococcal disease are those:







or
to
of
of

with functional and anatomical asplenia

with immunosuppression
with complement deficiency
who travel to high-risk endemic areas
who have contact with infected individuals
who are university students under the age of 25 years.

The vaccines are safe to give to women who are

breastfeeding. The two available vaccines are Meningococcal
Group C conjugated vaccine (MenC) and quadrivalent
(ACW135Y) polysaccharide vaccine. The UK Department of
Health recommends that the conjugated vaccine be used in
preference to the polysaccharide vaccine because it provides
better and longer lasting protection.30

Pneumococcal conjugated vaccine

The use of the pneumococcal conjugated vaccine is limited
among women of child bearing age.31 Ideally the vaccine
should be given prior to conception but the indication for
administration (patients with functional or anatomical
asplenia, sickle cell disease, splenectomy or patients with
HIV) are not altered by pregnancy.32

Typhoid
Pregnant women should be advised to avoid travel to typhoid
endemic areas but may be immunised with the inactive
parenteral vaccine if such exposure is unavoidable.33

Rabies
Rabies is virtually always fatal. Given the potentially
disastrous consequences of inadequately managed rabies
exposure to both mother and baby and the fact that it is an
inactivated viral vaccine, pregnancy is not considered a
contraindication to postexposure prophylaxis.34,35 Preexposure prophylaxis against rabies may be justified during
pregnancy, where the risk of exposure to rabies is substantial.

Yellow fever
Yellow fever is associated with a high case fatality rate. If
travel is unavoidable and the risk of yellow fever is high,
immunisation with live attenuated viral vaccine may be
considered after discussion with an infectious disease

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Vaccination in pregnancy

specialist.36 Pregnancy is a precaution for yellow fever vaccine

administration, compared with other live vaccines which are
contraindicated in pregnancy.

individual is believed to outweigh the risk of harm to the

patients and the general population.

Conclusion
Breastfeeding and vaccination
Viral vaccines (both inactivated and live) administered to a
lactating woman do not affect the safety of breastfeeding
for women or their infants. Although there is a risk of
replication of the vaccine strain with live viral vaccines, the
majority of live viruses in vaccines have not been
demonstrated in human breast milk. Rubella vaccine
virus has been isolated in human milk, although the
virus does not usually affect the infant. Even if infection
does occur, it is well tolerated because the virus
is attenuated.
For mothers who are breastfeeding their infants,
inactivated,
recombinant,
subunit,
polysaccharide,
conjugated vaccines and toxoids pose no risk.
Breastfeeding women should be advised to avoid yellow
fever vaccine. However, where the risk of acquisition of
yellow fever is high, as in nursing mothers who cannot avoid
or postpone travel to areas endemic for yellow fever,
vaccination should not be withheld.
Thus, breastfeeding is not considered either a precaution
or a contraindication for most of the commonly used
vaccines. Furthermore, breastfeeding does not adversely
affect the success or the safety of the vaccination.37

Postpartum advice
The two vaccines that should be specifically administered
before discharge to protect the mother and the neonate are:13,38
 MMR vaccine women should be counselled to avoid
becoming pregnant for 28 days after vaccination.
 Varicella vaccine Varicella vaccination prepregnancy or
postpartum is an option that should be considered for
women who are found to be seronegative for VZV IgG. It
is a live attenuated vaccine administered in two separate
doses 48 weeks apart. If a woman of reproductive age is
vaccinated, she should be advised to avoid pregnancy for 1
month after each dose and to avoid contact with other
susceptible pregnant women should a postvaccination
rash occur.

Ethical issues
Although the fetus has no claim to legal rights, use of the
mother as a medium to protect her fetus has been generally
accepted by society.
Compulsory vaccination of healthcare professionals may
be an ethically justified approach where the autonomy of the

262

The exceptional public health impact of vaccination is

indisputable. As the primary clinicians responsible for the
care of pregnant women, midwives and obstetricians are
uniquely placed to improve the health outcomes related to
vaccine preventable diseases in the pregnant population and
in the neonate. There is an urgent, pressing need for
consolidated and robust national guidance on vaccination
in pregnancy to guide healthcare professionals to provide
comprehensive, holistic antenatal care to pregnant women.

Disclosure of interests:
The authors have no conflicts of interest to declare.

Contribution of authorship:
PSA is the main author responsible for conception and
design, drafting the article and final approval. SK and AS
revised the article and are responsible for the final version.

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