Clinical Expert Series

Vaccinations for Pregnant Women

Geeta K. Swamy, MD, and R. Phillips Heine, MD

In the United States, eradication and reduction of vaccine-preventable diseases through

immunization has directly increased life expectancy by reducing mortality. Although immuni-
zation is a public priority, vaccine coverage among adult Americans is inadequate. The Institute
of Medicine, the Community Preventive Services Task Force, and other public health entities
have called for the development of innovative programs to incorporate adult vaccination into
routine clinical practice. Obstetrician–gynecologists are well suited to serve as vaccinators of
women in general and more specifically pregnant women. Pregnant women are at risk for
vaccine-preventable disease-related morbidity and mortality and adverse pregnancy outcomes,
including congenital anomalies, spontaneous abortion, preterm birth, and low birth weight. In
addition to providing direct maternal benefit, vaccination during pregnancy likely provides
direct fetal and neonatal benefit through passive immunity (transplacental transfer of maternal
vaccine-induced antibodies). This article reviews: 1) types of vaccines; 2) vaccines specifically
recommended during pregnancy and postpartum; 3) vaccines recommended during pregnancy
and postpartum based on risk factors and special circumstances; 4) vaccines currently under
research and development for licensure for maternal–fetal immunization; and 5) barriers to
maternal immunization and available patient and health care provider resources.
(Obstet Gynecol 2015;125:212–26)
DOI: 10.1097/AOG.0000000000000581

V accine-preventable diseases are defined as those

infectious diseases for which an effective preventive
vaccine exists and may be prevented by vaccinating
decade.3 Infectious diseases remain a major cause of
adult morbidity and mortality, with well more than
50,000 adults dying each year from vaccine-
individuals per standard recommendations.1 In the preventable diseases and associated complications.3
United States, eradication and reduction of vaccine- National immunization recommendations cur-
preventable diseases through immunization have directly rently target 17 vaccine-preventable diseases across
increased life expectancy by reducing infectious- the lifespan. However, adult coverage for most rou-
disease mortality.2 For example, deaths from inva- tinely recommended vaccines is suboptimal and well
sive pneumococcal disease, hepatitis A and B, and below Healthy People 2020 goals.4 In 2011, only 20%
varicella have dramatically declined over the past of adults were appropriately vaccinated against pneu-
mococcus; 12.5% against tetanus, diphtheria, and per-
From the Department of Obstetrics and Gynecology, Division of Maternal-Fetal tussis or hepatitis A; 35% against hepatitis B; and 43%
Medicine, Duke University, Durham, North Carolina.
of women against human papillomavirus.5 Consider-
Continuing medical education for this article is available at http://links.lww.
com/AOG/A579. able increases in vaccination coverage are needed to
Corresponding author: Geeta K. Swamy, MD, Duke Maternal-Fetal Medicine,
significantly reduce or eradicate the incidence of
2608 Erwin Road, Suite 200, Durham, NC 27705; e-mail: geeta.swamy@ vaccine-preventable diseases in adults. The Institute of
duke.edu. Medicine, the Community Preventive Services Task
Financial Disclosure Force, and other public health entities have called for
Dr. Swamy has received past support from GlaxoSmithKline for consultant and
speaker activities that ended in March 2012. Dr. Heine has been a consultant
the development of innovative programs and incorpo-
and speaker for GlaxoSmithKline and a speaker for Merck, Inc. Both authors ration of adult vaccination into routine clinical prac-
have received research funding from the National Institutes of Health, the Centers tice.6,7 With approximately 32,000 obstetrics and
for Disease Control and Prevention, the American College of Obstetricians and
Gynecologists, and GlaxoSmithKline to conduct vaccine-related research.
gynecology offices in the United States, integration of
adult immunizations into routine obstetric and gynecol-
© 2014 by The American College of Obstetricians and Gynecologists. Published
by Lippincott Williams & Wilkins. ogy practice is one approach that would reach the vast
ISSN: 0029-7844/15 majority of women across the lifespan.

212 VOL. 125, NO. 1, JANUARY 2015 OBSTETRICS & GYNECOLOGY

 Obstetrician–gynecologists (ob-gyns) provide more ob-gyns have the potential to greatly affect the health
general medical care to women than either family and well-being of mothers and infants through mater-
practice or internal medicine providers and thus nal immunization and contribute to the public health
would have opportunities to incorporate vaccination campaign for adult vaccine coverage. This article de-
into standard clinical care.8 Moreover, ob-gyns spe- scribes: 1) types of vaccines; 2) vaccines specifically
cifically care for pregnant women who, along with recommended during pregnancy and postpartum; 3)
their fetuses, are particularly vulnerable to vaccine- vaccines recommended during pregnancy and post-
preventable disease-related complications. Pregnant partum based on risk factors and under special cir-
women are at extremely high risk for influenza- cumstances; 4) vaccines currently under research
related morbidity and mortality including adverse and development for licensure for maternal–fetal
pregnancy outcomes (fetal growth restriction, pre- immunization; and 5) barriers to maternal immuniza-
term birth, and fetal demise).9–13 Rubella and vari- tion and available resources.
cella infections during pregnancy can lead to
complex congenital anomalies. Although congenital TYPES OF VACCINES
hepatitis B does not cause malformations, vertical Based on laboratory methods, vaccines are classified
transmission is associated with lifelong disease and as live attenuated, inactivated or killed, toxoid, sub-
long-term sequelae. Thus, immunization before con- unit, or conjugate vaccines (Table 1). Live attenuated
ception would be ideal for the prevention of vaccine- vaccines may contain living organisms that have been
preventable diseases associated with congenital disease. weakened or altered so as not to cause infection.19,20
However, for vaccine-preventable diseases associated Disease-causing pathogens are manipulated in the lab-
with adverse maternal, fetal, or neonatal health, immu- oratory through multiple rounds of tissue culture or
nization during pregnancy provides not only maternal animal embryos, mutagenesis, or targeted genetic al-
benefit, but may have the added benefit of direct neo- terations to specifically select very low virulent strains.
natal protection. Passive immunity—transplacental Manipulated pathogens do not cause overt human
immune globulin G antibody transfer from vaccinated disease but adequately stimulate an immune response
mother to fetus—provides infant protection for up to 6 so that healthy people mount an immune response
months of life.14,15 Maternal immunization is particu- nearly equivalent to what would follow natural expo-
larly important when considering vaccine-preventable sure or infection. Although technically possible for
diseases from which we have no other options for pro- clinical infection to occur after live attenuated vacci-
tecting young infants, such as influenza and pertussis. nation, it is extremely uncommon, and any illness that
Specifically, influenza vaccine is not licensed for use occurs is typically much milder than natural infection
before 6 months of age, and adequate antipertussis anti- and is classified as an adverse reaction. However,
bodies are only achieved after two to three doses of immunocompromised individuals are at risk for
diphtheria and tetanus toxoids and acellular pertussis unregulated pathogen replication followed by
vaccine by 6 months of age.16 severe-to-fatal infection and cannot receive live atten-
Ob-gyns are well-positioned to screen and vacci- uated vaccines. Similarly, live attenuated vaccines are
nate pregnant women against vaccine-preventable contraindicated during pregnancy as a result of the
diseases, having demonstrated their capability theoretical risk of perinatal infection resulting in con-
through the near eradication of congenital rubella in genital disease, eg, rubella or varicella.
the United States through routine antenatal surveil- Inactivated or killed vaccines are created by
lance and postpartum vaccination. Furthermore, inactivating a pathogen using heat or chemicals like
ob-gyns were heavily involved in the extensive formalin or formaldehyde.19,20 Inactivating processes
administration of H1N1 vaccine to pregnant women destroy the pathogen’s ability to replicate, because it
during the 2009 pandemic and have continued their does not contain any living or infectious particles and
efforts to increase maternal influenza vaccination, thus cannot result in clinical infection. Certain bacte-
exceeding 50% coverage for the first time in 2012– ria cause disease by producing a toxin rather than
2013.17 Among the vaccines recommended by the by direct bacterial interaction, as seen in Clostridium
Centers for Disease Control and Prevention (CDC) tetani. Vaccines against such diseases, called toxoid
for adults, two are directly recommended for admin- vaccines, are similarly created by inactivating the tox-
istration during pregnancy, four are recommended in ins using heat or chemicals. Inactivated and toxoid
pregnancy based on additional risk factors, and two vaccines maintain their ability to generate an immune
are specifically recommended during the postpartum response, albeit less robust than the response after live
period.18 With nearly 4 million U.S. births each year, attenuated vaccines. Antibody levels wane over time,

VOL. 125, NO. 1, JANUARY 2015 Swamy and Heine Vaccinations for Pregnant Women 213
Table 1. Current Vaccine Recommendations for Pregnant Women

General Adult
Vaccine Vaccine Type Pregnancy Recommendation Recommendation

Vaccines recommended
for all pregnant
women
Influenza Inactivated viral subunit or 1 dose of inactivated vaccine 1 dose of inactivated or live
live attenuated viral administered during flu season, attenuated vaccine administered
recombinant any gestational age annually during flu season
Tdap/Td Tetanus and diphtheria— 1 dose Tdap after 20 wk, preferably Substitute 1 lifetime dose of Tdap
inactivated toxoids; approximately 28 wk, regardless of for Td booster; return to Td
acellular pertussis— prior Tdap receipt booster every 10 y or sooner if
inactivated subunit exposure occurs
Vaccines recommended
for postpartum
women
(contraindicated
during pregnancy)
MMR Live attenuated viral 1 dose immediately postpartum if 1–2 doses, lifetime; additional 1
rubella nonimmune or equivocal dose older than 55 y if risk factor
present
Varicella Live attenuated (viral) 1 dose immediately if varicella 2 doses, lifetime
nonimmune
Vaccines recommended
for pregnant women
with risk factors or
special
circumstances
Hepatitis A Inactivated whole-cell 2 doses if risk of infection outweighs 2 lifetime doses
viral theoretical risk of vaccine
Hepatitis B Inactivated viral 3 doses if previously unvaccinated or 3 lifetime doses
recombinant subunit at high risk of exposure
Pneumococcal Inactivated bacterial 1 dose if risk factor present 1–2 doses if risk factor present; 1
polysaccharide dose for all individuals 65 y or
older
Meningococcal Inactivated bacterial 1 dose if risk factor present Can be used for children younger
polysaccharide than 2 y and adults older than
55 y and during epidemics
Yellow fever Live attenuated viral 1 dose if travel to endemic regions 1 dose for travel to endemic
and risk of infection outweighs regions
theoretical risk of vaccine
Japanese encephalitis Live attenuated viral 1 dose if travel to endemic regions 1 dose for travel to endemic
and risk of infection outweighs regions
theoretical risk of vaccine
Typhoid Live attenuated bacterial Not recommended owing to lack of For travel to endemic regions
recombinant data
Anthrax Inactivated subunit Postexposure prophylaxis for all Preexposure prophylaxis if risk
pregnant women; preexposure factor; postexposure prophylaxis
prophylaxis is not recommended for all adults
owing to lack of data
Rabies Inactivated whole-cell Postexposure prophylaxis; consider Preexposure prophylaxis if risk
viral preexposure prophylaxis if risk of factor; postexposure prophylaxis
exposure is very high for all adults
Tdap, tetanus, diphtheria, acellular pertussis; Td, tetanus, diphtheria; MMR, measles, mumps, and rubella.

thus requiring multiple dosing, booster dosing, or a protective immune response.19,20 One method for
both to maintain adequate protection. creating a subunit vaccine is by isolating a specific anti-
Subunit vaccines contain fragments of the patho- genic protein like with acellular pertussis vaccine. Alter-
gens they protect against, which subsequently provoke natively, several subunit vaccines are created through

214 Swamy and Heine Vaccinations for Pregnant Women OBSTETRICS & GYNECOLOGY
genetic engineering or recombination. For hepatitis B randomized study of 340 pregnant women revealed
vaccine, as an example, a gene encoding for a patho- a 36% reduction in influenza illness.14 A large
gen-specific protein is inserted into another virus or cell population-based study from Norway revealed a 70%
culture. For human papillomavirus vaccine, expression reduction in flu illness in immunized mothers, suggesting
of a single human papillomavirus protein results in pro- an even greater maternal benefit than previously
duction of virus-like particles. Virus-like particles con- thought.10 In addition to maternal benefits, inactivated
tain no actual viral genetic material and thus cannot influenza vaccine during pregnancy carries significant
cause infection. After vaccination, the immune system fetal and neonatal benefits. Maternal immunization has
recognizes the expressed proteins from recombinant been associated with an increase in birth weight and
vaccines and develops protective antibodies against a reduction in low birth weight, preterm birth, and
the target pathogen. Conjugate vaccines are similar to fetal death.10,14 Furthermore, a recent randomized
recombinant vaccines except they are created by chem- trial of third-trimester maternal inactivated influenza
ically combining pieces of the bacterial coat with a car- vaccine compared with pneumococcal vaccine led to
rier protein. The bacterial components are unable to a 29% reduction in respiratory illness and a 63%
cause infection and require the carrier protein to stim- reduction in laboratory-confirmed flu among new-
ulate an adequate immune response. borns up to 6 months of age in the maternal inacti-
vated influenza vaccine group.14 These findings have
VACCINES RECOMMENDED FOR USE IN been confirmed in multiple population-based studies
PREGNANCY AND POSTPARTUM with confirmed flu cases reduced 39–47% and hospi-
Influenza talizations reduced up to 90% in infants up to 6
Influenza (flu) is an RNA virus with A and B serotypes months of age.25,26 It is unknown whether maternal
and is responsible for both endemic and pandemic flu immunization during the first or second trimester will
(Table 1). Both types are responsible for endemic flu, provide similar infant benefit. Future studies are
whereas type A, as a result of antigenic drift of its required to address gestational age timing of vaccina-
surface proteins hemagglutinin and neuraminidase, tion because timing of administration may differ for
is responsible for flu pandemics.21 In a single flu sea- maternal, fetal, or neonatal benefit.
son, it is estimated that 20% of the U.S. population Occurring in more than 90% of infected individuals,
contracts the illness, with the number increasing to the most common symptoms of flu are fever and cough
50% during pandemics. Each year, 20% of pregnant with a sore throat, myalgia, and headache occurring less
women will develop upper respiratory-like illness with commonly in approximately 30–50% of patients. Preg-
10% having laboratory-confirmed flu.22 nant women who present with fever above 100.0°F,
Pregnant women infected with flu have increased exhibit either sore throat or cough, and have no other
rates of hospitalization, cardiopulmonary complica- explanatory causes can be presumptively diagnosed
tions, and death when compared with the general with the flu, and treatment should be initiated. Rapid
population.12 Complications are further increased tests are available, but poor sensitivity limits usefulness
during pandemics, as seen during the 2009 H1N1 out- in high-risk populations such as pregnant women.27
break when 5% of all related deaths occurred in preg- Confirmatory tests such as culture or polymerase chain
nant women, yet they only encompass 1% of the total reaction are extremely sensitive for the diagnosis of the
population.11 Multiple complications including spon- flu but the delay in result reporting and lack of wide-
taneous abortion, stillbirth, neonatal death, preterm spread availability limit their utility. According to the
birth, and low birth weight have been reported among CDC, treatment should not be delayed while waiting
influenza-infected women and likely correlate with for a result.28 However, confirmatory testing remains
disease severity.13 During the 2009 pandemic, the pre- important for public health surveillance of serotype
term birth rate increased threefold among infected and identification of drug resistance patterns.
pregnant women admitted to the hospital.23 Treatment of flu during pregnancy consists of oral
Immunization is the best strategy for flu prevention (oseltamivir) or inhaled (zanamivir) therapy. Oselta-
as supported by the current CDC recommendation that mivir is preferred in pregnancy as a result of its safety
all pregnant women receive inactivated influenza vac- profile and convenience unless high levels of oselta-
cine during flu season. Live attenuated vaccine is mivir resistance are encountered; then health care
contraindicated in pregnancy, although inadvertent providers should shift preference to inhaled zanami-
administration during the first trimester has not been vir.29 Treatment should be initiated as rapidly as pos-
associated with adverse outcomes.24 Regarding inacti- sible, because delay in initiation (more than 2 days of
vated influenza vaccine efficacy in pregnancy, a recent symptom onset) has been associated with worsening

VOL. 125, NO. 1, JANUARY 2015 Swamy and Heine Vaccinations for Pregnant Women 215
morbidity (ie, intensive care unit admission, mechan- successfully implemented. For example, new fathers
ical intubation, and death). and other close contacts are not routinely receiving
diphtheria and reduced tetanus toxoids and acellular
Tetanus, Diphtheria, and Pertussis pertussis vaccine.36 Moreover, it is unlikely that post-
Vaccination against diphtheria, tetanus, and pertussis partum maternal immunization as a sole strategy is
is included in the standard U.S. childhood vaccination adequate to prevent infant pertussis.37 In October
schedule with the diphtheria, tetanus, acellular per- 2011, the CDC’s Advisory Committee on Immuniza-
tussis series starting at 2 months of age. C tetani re- tion Practices considered current safety data, the
leases the tetanospasmin neurotoxin, which causes potential for protection against infant pertussis from
tetanus infection or prolonged muscular contraction. transplacentally transferred maternal antibodies, and
Corynebacterium diphtheriae causes an upper respiratory a decision analysis suggesting vaccination during
infection called diphtheria. Tetanus and diphtheria pregnancy is superior to postpartum administration.
infections are nearly eradicated in the United States During this meeting, the CDC changed their “cocoon-
through routine decennial Td booster dosing across ing” recommendation to administration of diphtheria
the lifespan and exposure-related administration. and reduced tetanus toxoids and acellular pertussis
However, pertussis—a respiratory infection caused by vaccine to unimmunized women during the late sec-
Bordetella pertussis—has not followed a similar pattern. ond or third trimester of pregnancy. Immediate post-
Since the 1980s, pertussis has been on the rise in the partum diphtheria and reduced tetanus toxoids and
United States after many years of effective disease acellular pertussis vaccine vaccination should be
control and prevention. From less than 5,000 reported offered to unimmunized women who did not receive
cases in the early 1980s, pertussis reached to an all- diphtheria and reduced tetanus toxoids and acellular
time high of 48,277 cases in 2012 and dropped to pertussis vaccine during pregnancy.38,39 This was fol-
24,231 cases in 2013.30,31 It is unclear if the resurgence lowed by a swift adoption of CDC recommendations
is the result of mutations in the B pertussis bacteria, by the American College of Obstetricians and Gyne-
heightened awareness combined with improved cologists (the College) in March 2012, demonstrating
diagnostic testing and increased reporting, or rapid strong support by the College for interventions
waning of postacellular vaccination immunity.32,33 proven to benefit both mother and infant.
Although reported cases have increased in the general Very soon after ob-gyns began working to
population, pertussis-related morbidity and mortality implement office processes to administer diphtheria
disproportionately affect infants younger than 12 and reduced tetanus toxoids and acellular pertussis
months of age.34 Young infants usually are infected vaccine to unimmunized pregnant women in their
after exposure to a close contact, with 47–60% of cases practices, the CDC’s Advisory Committee on Immu-
resulting from exposure from infected parents.16 nization Practices voted unanimously in October 2012
Adults with pertussis are often unaware of their diag- to recommend diphtheria and reduced tetanus toxoids
nosis, given that many adults are either asymptomatic and acellular pertussis vaccine vaccination to all preg-
or have symptoms of a common cold. nant women regardless of her history of diphtheria
Innovative strategies are needed to prevent infant and reduced tetanus toxoids and acellular pertussis
pertussis given that infants do not have adequate vaccine receipt.40 Such aggressive action was taken
vaccine-induced protection against pertussis until at as a result of the record-breaking numbers of pertussis
least 6 months of age, after two to three diphtheria, cases and deaths, 48,277 and 20 in 2012, respec-
tetanus, acellular pertussis vaccine doses.16 One strat- tively.41 Although passive infant immunity has been
egy is to “cocoon” infants or decrease their risk of documented after maternal immunization,42 limited,
pertussis exposure by immunizing their close contacts statistically nonsignificant data have been extrapo-
against pertussis. In 2005, the CDC recommended lated to suggest that the optimal timing for diphtheria
that unvaccinated postpartum women and other close and reduced tetanus toxoids and acellular pertussis
contacts of newborns receive the diphtheria and vaccine is in the third trimester and at least 2 weeks
reduced tetanus toxoids and acellular pertussis vac- before delivery to allow for an adequate maternal
cine to decrease neonatal exposure to pertussis.35 antibody response. Although it is imperative that ob-
Despite some progress in diphtheria and reduced tet- gyns routinely administer diphtheria and reduced tet-
anus toxoids and acellular pertussis vaccine adminis- anus toxoids and acellular pertussis vaccine to all
tration during the immediate postpartum period, pregnant women to avoid potentially devastating infant
diphtheria and reduced tetanus toxoids and acellular pertussis, many questions regarding vaccine effective-
pertussis vaccine cocooning programs have not been ness, optimal timing of vaccine administration, infant

216 Swamy and Heine Vaccinations for Pregnant Women OBSTETRICS & GYNECOLOGY
antibody correlates of protection, and safety of repeated fetal harm or vaccine-induced infection is theoretical,
close-interval dosing in multiparous women remain un- the potential severe consequence of infection during
answered. Ongoing studies of diphtheria and reduced pregnancy outweighs the potential benefit of vaccina-
tetanus toxoids and acellular pertussis vaccine in preg- tion in the United States. The CDC Vaccine in Preg-
nancy will provide some of these answers.43,44 nancy Registry demonstrates no reported cases of
congenital rubella syndrome after unintentional first-
Measles–Mumps–Rubella trimester vaccination.48 Thus, inadvertent measles–
Routine childhood vaccination and young adult mumps–rubella vaccination during pregnancy should
booster dosing have dramatically diminished the not be considered grounds for pregnancy termina-
incidence of measles, mumps, and rubella in the United tion.48 Preconception screening and measles–
States. Measles is a paramyxovirus that presents mumps–rubella administration are ideal for avoiding
routinely with rash, diarrhea, and otitis media along congenital rubella syndrome during the next future
with bronchopneumonia or encephalitis in severe pregnancy rather than awaiting screening and post-
cases. Infection during pregnancy increases the risk of partum administration. However, screening for
spontaneous abortion, preterm birth, and low birth rubella immunity should be included in the routine
weight.45 Mumps is another paramyxovirus that prenatal laboratory panel. All pregnant women who
presents with flu-like symptoms and bilateral parotitis are susceptible to rubella should be vaccinated imme-
and is associated with spontaneous abortion. Rubella is diately postpartum, thus reducing or eliminating risk
a togavirus that presents with more nonspecific symp- in subsequent pregnancies and neonatal exposure
toms including lymphadenopathy, arthralgias, fever, risk.47 Breastfeeding is not a contraindication for post-
and rash. Infection during pregnancy, especially in partum vaccination because any attenuated rubella
the first trimester, can be devastating. In the last U.S. virus excreted in breast milk and transmitted to the
rubella epidemic in 1964–1965, approximately 12.5 neonate results in asymptomatic infection.47
million rubella infections resulted in 11,250 spontane-
ous or therapeutic abortions, 2,100 neonatal deaths, Varicella
and 20,000 neonates born with congenital rubella syn- Varicella zoster virus, a member of the herpes virus
drome.46 Serious sequelae of congenital rubella syn- family, causes chicken pox. Illness usually presents as
drome include deafness, cataracts, cardiac defects, a pruritic rash for 4–7 days, during which time the
neurologic damage, and death. infected individual is highly contagious.49 Viral trans-
Although rubella cases dramatically declined mission occurs by direct contact with skin lesions or
over the past 40 years, inclusion of measles– inhalation of aerosolized particles. Infection during
mumps–rubella in the universal vaccination program pregnancy is associated with neonatal varicella or her-
occurred in 2004, after which elimination of endemic pes zoster and congenital varicella syndrome, which is
rubella virus transmission was documented in the characterized by skin scarring, limb hypoplasia, low
United States.46 From 2004 to 2012, 79 cases of birth weight, and numerous other anomalies.50 Con-
rubella infection and six cases of congenital rubella genital varicella syndrome occurs in 1–2% of cases of
syndrome were documented with all sources being maternal varicella infection with the greatest risk of
foreign import or unidentifiable. Three of the six con- occurrence associated with maternal infection from
genital rubella syndrome cases occurred in 2012 13 to 20 weeks of gestation.
among mothers who had been in Africa during early Varicella vaccine, a live attenuated vaccine, was
pregnancy. Thus, measles–mumps–rubella vaccina- first introduced in 1995, at which time there were
tion continues to be of high relevance to obstetric care more than 4 million cases, more than 10,000 hospital-
given the increasing immigration and global mobility izations, and approximately 150 deaths per year in the
of the U.S. population. United States.51 Ten years after national recommen-
After two childhood measles–mumps–rubella dations to administer a two-dose regimen as part of
doses, college or graduate students should receive the routine childhood vaccination schedule, disease
additional doses or have documented immunity incidence has dropped by 90%, with hospitalizations
against all three viruses.47 Given that measles– and deaths down by 71% and 97%, respectively. In
mumps–rubella is a live attenuated vaccine and con- 2003–2004, there were eight reported deaths result-
traindicated in pregnancy, pregnancy status should be ing from varicella, six of which occurred in children.
queried among all women of childbearing potential Thus, vaccination is the most effective means of pre-
before vaccination with counseling to avoid concep- venting varicella infection and congenital varicella syn-
tion for 4 weeks postvaccination. Although the risk of drome. However, varicella vaccine is contraindicated

VOL. 125, NO. 1, JANUARY 2015 Swamy and Heine Vaccinations for Pregnant Women 217
in pregnancy as a result of its live attenuated formula- not sufficient data to deem hepatitis A virus vaccine
tion. Analogous to rubella vaccination in early preg- safe for use during pregnancy, the current vaccine
nancy, no cases of congenital varicella syndrome formulation is inactivated with no live virus compo-
have been reported after inadvertent varicella vaccina- nents and thus extremely unlikely to cause infection
tion during pregnancy based on the VARIVAX Preg- or harm to the mother, fetus, or infant. Pregnant
nancy Registry co-sponsored by Merck and Company, women should receive hepatitis A virus vaccine when
Inc., and the CDC. Therefore, the CDC recommends the risk of infection outweighs the theoretical risk of
that unintentional vaccination in pregnancy does not administration of an inactivated vaccine.54
imply a need for pregnancy termination.49,52 More-
over, preconception varicella vaccine administration Hepatitis B
is ideal to avoid congenital varicella syndrome during Hepatitis B virus, a DNA virus, causes acute liver
the next future pregnancy. Varicella immunity should infection with inflammation, vomiting, and jaundice.
be established for all pregnant women during early Hepatitis B virus can be self-limiting or achieve
pregnancy by self-reported history of infection, history a chronic carrier state associated with long-term con-
of vaccination, or documented serologic immunity. All sequences including cirrhosis, liver cancer, liver failure,
pregnant women who are susceptible to varicella zoster and death. Hepatitis B virus is transmitted after close
virus infection should be counseled about the risk of contact with infected blood and bodily fluids. The
perinatal infection and instructed to immediately con- current hepatitis B virus vaccine is a recombinant DNA
tact their health care provider in case of exposure. formulation based on the hepatitis B surface antigen
Documented exposure should be followed by prompt envelope protein. A three-vaccine series is highly
administration of varicella zoster immunoglobulin.53 effective for disease prevention, providing an indefinite
Antivirals such as acyclovir should be used for actual protective antibody response in greater than 90% of
chicken pox infection with consideration of hospital vaccinated individuals.56 Hepatitis B virus infections
observation for development of varicella-related com- decreased 64% over the past decade, dropping from
plications such as respiratory disease.53 Mothers who 8,036 cases in 2000 down to 2,890 cases in 2011 as
are or suspected to be varicella zoster virus-susceptible a result of vaccine prevention.55
should receive two doses of vaccine postpartum—the Hepatitis B virus during pregnancy, both the
first immediately postpartum and the second 4–8 chronic carrier state as well as primary infection, is
weeks later.49 concerning for the risk of vertical transmission.
Perinatally acquired hepatitis B virus infection is
VACCINES RECOMMENDED IN PREGNANCY associated with the highest risk of developing chronic
AND POSTPARTUM BASED ON RISK FACTORS disease for the offspring. All pregnant women should
AND SPECIAL CIRCUMSTANCES be screened for hepatitis B surface antigen status as
Hepatitis A part of standard prenatal laboratory testing. At-risk
Hepatitis A virus, a RNA picornavirus, causes fever, neonates should be treated with hepatitis B immuno-
nausea, abdominal pain, and jaundice as a result of globulin prophylaxis and receive the first hepatitis B
acute, self-limiting liver infection (Table 1). Hepatitis virus vaccine dose within the first hours of life.57
A virus is transmitted through the fecal–oral route Such a regimen is an effective strategy against peri-
after close contact with infected individuals or con- partum transmission, which is the most common sce-
taminated food or drinks.54 First licensed in 1996, nario. However, in utero transmission can and does
widespread hepatitis A virus vaccination in the United occur, most likely in mothers who develop primary,
States began in 1999. From 2007 to 2011, the number acute hepatitis B virus infection in late pregnancy.58
of hepatitis A virus cases dropped from 2,979 to Therefore, hepatitis B virus vaccination is the best
1,398.55 Although hepatitis A virus vaccine is included preventive measure, including administration both
in the CDC childhood vaccination schedule at 12–23 preconception and during pregnancy. The three-
months of age, the CDC also recommends adult hep- dose hepatitis B virus vaccine series should be
atitis A virus vaccination for individuals deemed high initiated for pregnant women who have not been vac-
risk for hepatitis A virus exposure. Risk factors cinated previously and are at high risk of acquiring
include travel to endemic areas, men having sex with infection, namely those with one or more sexual part-
men, exposure to individuals with hepatitis A virus ner in the past 6 months, history of a hepatitis B virus-
infection or those receiving clotting factor concen- positive sexual partner or household contact, or
trates as a result of clotting factor deficiencies, and intravenous drug use.56 Safety data, although some-
exposure to biological specimens. Although there is what limited, have not demonstrated any association

218 Swamy and Heine Vaccinations for Pregnant Women OBSTETRICS & GYNECOLOGY
with adverse maternal or fetal outcomes, consistent pneumococcal conjugate vaccine or 23-serotype poly-
with the expected safety profile of a recombinant inac- saccharide vaccine during pregnancy.18 A systematic
tivated product that does not contain live virus.59 In review of six observational studies of 23-serotype
addition to vaccination and hepatitis B immunoglobu- polysaccharide vaccine in pregnancy demonstrated
lin, newly emerging data advocate for the use of anti- no increase in spontaneous abortion, teratogenicity,
viral therapy during the third trimester to prevent in or preterm labor.59 Furthermore, a randomized trial
utero transmission or prophylaxis failure.58 However, of 60 pregnant women receiving 23-serotype polysac-
given the uncertain risks of antivirals during pregnancy, charide vaccine at 35 weeks of gestation demonstrated
treatment is being considered only for pregnant women no safety concerns or adverse outcomes.62 Maternal
with advanced disease. Treatment may consist of lam- 23-serotype polysaccharide vaccine administration re-
ivudine, telbivudine, or tenofovir but should only be sults in protective maternal antibody titers for up to 12
considered in conjunction with a hepatology specialist. months postpartum and significantly increases neona-
tal antibody titers at delivery. However, it is unknown
Pneumococcal Disease if passive immunity results in disease protection for
Streptococcus pneumoniae (pneumococcus) is a Gram- the infant. Per the CDC’s adult immunization sched-
positive bacterium associated with significant morbid- ule, 23-serotype polysaccharide vaccine should be
ity and mortality related to pneumonia, bacteremia, administered during pregnancy for women who have
meningitis, and otitis media.60 Approximately a medical risk factor(s), which likely affects a substan-
900,000 U.S. individuals get pneumococcal pneumo- tial number of women given the increasing incidence
nia, resulting in 400,000 hospitalizations and a 5–7% of obesity and related chronic conditions in the
mortality rate annually. There are 12,000 cases of bac- United States.18
teremia and 3,000 cases on meningitis, which carries
a mortality rate of 10–15%. Significant reductions in Meningococcal Disease
pneumococcal disease and related deaths occurred Approximately 1,000 individuals in the United States
after inclusion of the seven serotype pneumococcal will experience meningococcal disease (meningitis
conjugate vaccines in the U.S. childhood vaccination and sepsis) caused by an encapsulated bacterium
schedule in 2000 (200,000 cases and 13,000 deaths called Neisseria.63 Despite the use of antibiotics, the
prevented up to 2007).3 Furthermore, the introduction mortality rate is 10–15% with up to 20% of survivors
of 13 serotype pneumococcal conjugate vaccine in experiencing significant sequelae including limb am-
2010 resulted in an additional 20,000 cases and 2,000 putations, strokes, and neurocognitive abnormalities
deaths averted (Moore M. Update on effectiveness and such as seizures, deafness, and severe cognitive
impact of PCV13 use among U.S. children. Paper pre- impairment. There are two effective vaccines against
sented at Advisory Committee on Immunization Prac- meningococcal disease: tetravalent meningococcal
tice, October 23, 2013, Atlanta, Georgia.). From 2010 conjugate vaccine and a tetravalent polysaccharide
to 2012, there was an 88% reduction in childhood dis- vaccine. In 2000, the CDC recommended tetravalent
ease, which would be expected given that pneumococ- polysaccharide vaccine before college entry based on
cal conjugate vaccine is used exclusively in children. risk. Although effective, tetravalent polysaccharide
However, there was also a 47% reduction in adult vaccine does not confer long-lasting immunity as seen
pneumococcal disease, likely as a result of a reduction with tetravalent meningococcal conjugate vaccine.
in exposure. Furthermore, a broader 23-serotype poly- Therefore, in 2005, tetravalent meningococcal conju-
saccharide vaccine is recommended for children and gate vaccine was included in the U.S. childhood
adults with chronic medical conditions and all adults at vaccination schedule as a two-dose regimen for ado-
or older than 65 years of age to prevent invasive pneu- lescents aged 11–18 years. However, there are many
mococcal disease.61 Risk factors include chronic heart individuals who remain at high risk for the disease and
disease, chronic lung disease including asthma, preex- thus should be vaccinated with tetravalent meningo-
isting diabetes, cigarette smoking, alcoholism, chronic coccal conjugate vaccine based on risk factors, ie, in-
liver disease, cerebrospinal fluid leaks, cochlear im- dividuals living in close contact such as in dormitories
plants, congenital or acquired immunodeficiencies, dis- or military barracks, individuals with complement
eases requiring immunosuppressant therapy, sickle cell deficiencies and functional or anatomic asplenia, re-
disease and other hemoglobinopathies, and functional searchers with routine exposure to Neisseria meningitidis
or anatomic asplenia. isolates, and individuals living in hyperendemic areas.
Per the CDC, there are currently insufficient data Based on available efficacy and safety data, tetravalent
to support routine administration of 13 serotype meningococcal conjugate vaccine should be used

VOL. 125, NO. 1, JANUARY 2015 Swamy and Heine Vaccinations for Pregnant Women 219
through 55 years of age, whereas tetravalent polysac- travel to endemic areas and is often required before
charide vaccine is used after 55 years of age and for issuance of travel visas.66 Despite the general theoreti-
anyone at risk of exposure during an active disease cal contraindication to live attenuated vaccines during
outbreak. pregnancy, yellow fever vaccine is the exception.
Both tetravalent meningococcal conjugate vaccine Although there are limited data on the efficacy and
and tetravalent polysaccharide vaccine are inactivated safety of yellow fever vaccine during pregnancy, one
products and thus should not be associated with study that documented inadvertent vaccination of preg-
adverse maternal or fetal outcomes. However, the nant women during an outbreak demonstrated no asso-
limited data that are available on meningococcal ciation with teratogenesis, spontaneous abortion, or
vaccination during pregnancy is using tetravalent poly- preterm birth.67 Therefore, the CDC recommends yel-
saccharide vaccine and not tetravalent meningococcal low fever vaccine during pregnancy if a woman must
conjugate vaccine. A systematic review documented no travel and her risk of exposure and infection is high
association with maternal tetravalent polysaccharide enough (based on location, season, and activities
vaccine and teratogenesis, spontaneous abortion, or planned during travel) to outweigh any potential theo-
preterm birth.59 A study of third-trimester tetravalent retical risks of vaccination.68 Nonpregnant women of
polysaccharide vaccine vaccination demonstrated an childbearing potential should be counseled to avoid
appropriate maternal antibody response but selective conception for 4 weeks postvaccination.
transplacental antibody transfer with rapid waning Japanese encephalitis is another mosquito-borne
of infant immunity by 3 months of age.64 A recently RNA flavivirus that represents the most common
completed trial of more than 4,000 pregnant Malian vaccine-preventable disease cause of encephalitis in
women receiving influenza vaccine or tetravalent Asia.66 Less than 1% of infected individuals will
polysaccharide vaccine will provide much needed effi- manifest clinical symptoms of disease with mild dis-
cacy and safety data on tetravalent polysaccharide vac- ease limited to fever or aseptic meningitis. However,
cine in pregnancy.65 Given the lack of available safety serious illness presents with sudden onset of fever,
data on tetravalent meningococcal conjugate vaccine, headache, vomiting, and neurologic abnormalities
tetravalent polysaccharide vaccine is recommended for including generalized weakness, movement disorders
use during pregnancy based on risk factors described or acute paralysis, and seizures. Although the
previously.18 mortality rate is 20–30%, approximately 30–50% of
survivors will have serious neurocognitive and psychi-
Travel Vaccinations atric sequelae. An inactivated Japanese encephalitis
Absent any specific medical or pregnancy-related vaccine was licensed for use in the United States in
contraindications, healthy pregnant women are able 2009 and recommended by the CDC for travelers
to travel safely without significant restrictions. The who plan to spend 1 or more months in endemic areas
CDC recommends several vaccines for individuals or during disease outbreaks. Unfortunately, there are
traveling to areas with endemic vaccine-preventable no adequate studies of the vaccine during pregnancy.
diseases.66 Therefore, pregnant women planning As a result of the lack of adequate data, the CDC has
international travel should be advised to search the not made a specific recommendation on the use of
CDC travel web site, which provides up-to-date Japanese encephalitis vaccine during pregnancy.18
country-specific immunization recommendations However, the CDC recommends that Japanese
and aids in risk factor determination. Three travel- encephalitis vaccination should be considered for
related vaccine-preventable diseases that are frequently pregnant women planning longer-duration travel to
encountered are yellow fever, Japanese encephalitis, endemic areas when the theoretical risk of immuniza-
and typhoid fever. tion is outweighed by risk of infection.69
Yellow fever, a mosquito-borne disease caused by Typhoid fever is a life-threatening disease caused
an RNA flavivirus, is largely an asymptomatic infec- by the bacterium Salmonella typhi and is responsible for
tion. However, common symptoms are sudden onset approximately 5,700 U.S. cases each year.70 Approxi-
of fever and headache with less common symptoms of mately 75% of cases are contracted during international
photophobia, arthralgias, myalgias, vomiting, and epi- travel because typhoid fever is quite common in the
gastric pain. Severe infection is associated with multi- developing world and affects more than 21 million peo-
system organ failure, hemorrhage, and death. Yellow ple annually. Infected individuals usually present with
fever is endemic to tropical areas in South America and fever, fatigue, headache, and anorexia, whereas severe
sub-Saharan Africa. Thus, live attenuated yellow disease is associated with intestinal hemorrhage and
fever vaccine is recommended for individuals planning death. There are two vaccines against S typhi currently

220 Swamy and Heine Vaccinations for Pregnant Women OBSTETRICS & GYNECOLOGY
available in the United States, which are a live attenu- maternal rabies vaccination and spontaneous abortion,
ated oral vaccine and a polysaccharide vaccine, both of teratogenesis, or preterm birth.73,74 Thus, the CDC
which are acceptable for adults traveling to endemic recommends that postexposure prophylaxis with vacci-
areas. Unfortunately, there are no data supporting the nation and human rabies immunoglobulin should be
efficacy and safety of either vaccine in pregnancy. The administered to any pregnant woman after a moder-
CDC has made no formal, specific recommendation on ate-risk or high-risk exposure to rabies. Preexposure
the use of typhoid vaccines during pregnancy. prophylaxis in pregnancy can be considered if the
risk of exposure is deemed high.
Zoonotic Vaccine-Preventable Diseases
Bacillus anthracis, a spore-forming bacterium, causes VACCINES CURRENTLY UNDER RESEARCH
the zoonotic infection anthrax. Clinical manifestation AND DEVELOPMENT FOR LICENSURE FOR
depends on the exposure route (infected animal-to- MATERNAL–FETAL IMMUNIZATION
animal tissue contact or bacterial spore exposure) To date, vaccines in the United States are not specifically
and presents as cutaneous, injection (contaminated licensed or targeted for use during pregnancy. However,
needle use), gastrointestinal, or inhalation anthrax vaccines aimed at fetal–infant immunization are in vary-
with the latter two forms having high morbidity and ing stages of research and development for which the
mortality.71 Because B anthracis spores can be aerosol- target population will be pregnant women. Two exam-
ized and remain viable for a long time, anthrax has ples are group B streptococcus (GBS) and respiratory
been identified as a potentially serious and deadly syncytial virus. Group B streptococcus is the leading
biological weapon. The inactivated subunit anthrax cause of invasive infection during the first 90 days of life
vaccine adsorbed is available in the United States. and is the predominant cause of neonatal sepsis and
Preexposure vaccination is recommended by the meningitis, even in the setting of intrapartum antibiotic
CDC for individuals at high risk of exposure, ie, prophylaxis.75 From 1993 to 2008, intrapartum antibi-
military personnel, environmental investigators, otic prophylaxis reduced the incidence of early-onset
emergency responders, and postal processing staff. neonatal GBS infection from 1.7 to 0.28 cases per
However, preexposure anthrax vaccine adsorbed is 1,000 live births but had no effect on late-onset GBS
not recommended during pregnancy given the low disease in the United States.76 Given the significant
risk for exposure. Pregnancy is a Department of unmet need of late-onset disease (0.29–0.47 per 1,000
Defense exemption for preexposure prophylaxis with live births) and evidence of protection in the setting of
vaccination recommended postpartum. For postexpo- passive immunity,75,77 a GBS vaccine could be a more
sure prophylaxis, individuals should be vaccinated effective and reliable way to prevent both early- and late-
with anthrax vaccine adsorbed followed by 60 days onset disease. Moreover, a regimen of screening plus
of antimicrobial therapy.71 Although preexposure intrapartum antibiotic prophylaxis is neither feasible
anthrax vaccine adsorbed is not routinely recommen- nor affordable in the developing world where invasive
ded, postexposure prophylaxis is recommended and GBS disease remains a significant contributor to
should be administered to any pregnant woman with neonatal mortality and adverse pregnancy outcomes.
an anthrax exposure. A promising trivalent conjugated GBS vaccine is cur-
Contact with the saliva or central nervous system rently in phase II and III trials in pregnant women aimed
tissue of an individual or animal infected with rhabdo- at providing passive immunity to young infants.78
virus results in rabies infection. Rabies initially presents Respiratory syncytial virus is a RNA paramyxo-
with flu-like symptoms followed by neurologic abnor- virus named for how its surface F-proteins cause
malities and ultimately death if left untreated. Vacci- respiratory cell membranes to merge or form syncy-
nation of household pets is the most effective method tia. In the United States, 60% of infants will be
of human rabies prevention.72 There are two inacti- infected during their first respiratory syncytial virus
vated rabies vaccines available for human use in the season.79 Naturally induced immunity wanes over
United States and are recommended for individuals at time so that people can be repeatedly infected over
high risk of exposure, ie, veterinarians, animal han- the lifespan. Infection may be asymptomatic or simi-
dlers, and travelers to endemic areas. Postexposure lar to a cold but may cause severe disease in the
prophylaxis includes either rabies vaccine in conjunc- elderly. Respiratory syncytial virus is the most com-
tion with human rabies immunoglobulin, although mon cause of bronchiolitis and pneumonia during the
human rabies immunoglobulin is not necessary in in- first year of life, often necessitating hospitalization and
dividuals who have been previously vaccinated. Lim- resulting in recurrent wheezing. Given that infection
ited studies have shown no association between with this ubiquitous virus is unavoidable, a preventive

VOL. 125, NO. 1, JANUARY 2015 Swamy and Heine Vaccinations for Pregnant Women 221
vaccine would be ideal. A formalin-inactivated vac- between vaccines and complicated, multietiologic
cine was developed and studied in the 1960s but health outcomes such as autism spectrum disorders
was not efficacious and was associated with enhanced in children. Research to date involving more than
disease among vaccinated children.80 At present, the 100,000 children that has been vetted by the Institute
only preventive therapy available is palivizumab, an of Medicine, CDC, World Health Organization,
effective yet costly monoclonal antibody that is given American Academy of Pediatrics, and numerous
as monthly injections during the respiratory syncytial other agencies has very convincingly shown that there
virus season. Given the significant cost and need for is no such association between vaccines and
repeated dosing, palivizumab is restricted for use in autism.88,89 On the contrary, these studies have further
high-risk infants, namely preterm infants, those with supported the safety and effectiveness of vaccines in
bronchopulmonary dysplasia, or those born with con- reducing infectious disease and improving overall
genital heart or airway defects. A recombinant respi- health. Continued research on the overall health ef-
ratory syncytial virus vaccine is currently in phase II fects and safety of vaccines is warranted.
clinical and dose-ranging trials in nonpregnant Furthermore, ob-gyns who are concerned about
women with plans for a phase I trial in pregnant potential liability related to vaccination providers can
women in the near future.81 be reassured by the protection provided through the
National Childhood Vaccine Injury Act, which covers
BARRIERS TO VACCINATION IN PREGNANCY all vaccines that are included in the childhood
AND PATIENT–PROVIDER RESOURCES vaccination schedule regardless of who actually re-
Although national vaccination programs have led to ceives the vaccine, including adults and pregnant
significant declines in vaccine-preventable diseases in women. To aid all health care providers in safely
the United States, meeting the Healthy People 2020 administering vaccines, the CDC maintains a Vaccine
objectives for adult vaccination remains a daunting Information Statement for every vaccine licensed
task. Acceptance of vaccination during pregnancy is for administration in the United States. A Vaccine
affected by questions of maternal–fetal safety. Qualita- Information Statement informs health care providers
tive research involving patients and health care pro- and vaccinees about the benefits and risks of a specific
viders suggests that common perceived barriers include vaccine and is required by the National Childhood
fear of adverse pregnancy outcomes, fear of vaccine- Vaccine Injury Act to be given to all vaccinees (or
transmitted infection, lack of awareness of national rec- their parent or legal representative) before vaccina-
ommendations, lack of health care provider recommen- tion. Ob-gyns and nurses should be familiar with the
dation, inconvenience of vaccination, and concerns information contained in the Vaccine Information
about insurance coverage.82,83 For progress to occur, it Statements for any vaccines administered in their
is imperative that ob-gyns play an active role in over- office so that they can effectively screen and counsel
coming such barriers, as evidenced by pregnant women their patients on any vaccine contraindications, risks,
being five to 50 more likely to accept a vaccine if directly and benefits. Ob-gyns should be aware of additional
recommended by their health care provider.84–86 To aid tools in the event that an adverse event does occur in
ob-gyns and patients, the College publishes and main- a pregnant woman, which are the Vaccine Adverse
tains up-to-date Committee Opinions on specific vac- Event Reporting System and the Clinical Immuniza-
cines and guidance on implementing vaccination tion Safety Assessment Project. Cosponsored by the
processes into obstetrics–gynecologic practice. In 2011, CDC and the U.S. Food and Drug Administration,
the College launched the Immunization for Women Vaccine Adverse Event Reporting System is a national
web site, which provides up-to-date information on postmarketing national vaccine safety and side effect
vaccine recommendations, safety, and hyperlinks to surveillance program initiated after the National
College Committee Opinions, educational materials, Childhood Vaccine Injury Act.90 Anyone can submit
and frequently asked questions, further demonstrating a Vaccine Adverse Event Reporting System report,
the College’s commitment to immunization of women because it is considered a public health entity and
across the lifespan.87 Immunizationforwomen.org also does not require individual authorization per Health
provides hyperlinks to numerous highly informative, Insurance Portability and Accountability Act criteria.
user-friendly resources such as the CDC, Immuniza- With more than 200,000 reports since its inception in
tion Action Coalition, and the National Vaccine Pro- 1990 (mostly mild side effects), Vaccine Adverse
gram Office. Event Reporting System has demonstrated its public
Specifically regarding vaccine safety, there has health importance by identifying risks that are small
been much controversy over possible associations yet higher than chance alone, thus guiding national

222 Swamy and Heine Vaccinations for Pregnant Women OBSTETRICS & GYNECOLOGY
recommendations. Sponsored by the CDC’s Immuni- 5. Centers for Disease Control and Prevention (CDC). Nonin-
fluenza vaccination coverage among adults—United States,
zation Safety Office, Clinical Immunization Safety 2011. MMWR Morb Mortal Wkly Rep 2013;62:66–72.
Assessment provides a free-of-charge clinical evalua-
6. Increasing appropriate vaccination. Available at: http://www.
tion service of an adverse event that is unexpected or thecommunityguide.org/vaccines/index.html. Retrieved January
not explainable by available data.91 After obtaining all 3, 2014.
pertinent medical records, reviewing medical litera- 7. Vaccines for the 21st century: a tool for decision making.
ture and Vaccine Adverse Event Reporting System, Washington, DC: The National Academies Press; 2000.
vaccine safety experts from the CDC and the Clinical 8. Leader S, Perales PJ. Provision of primary-preventive health
Immunization Safety Assessment academic medical care services by obstetrician-gynecologists. Obstet Gynecol
1995;85:391–5.
centers review the clinical case in conjunction with
9. Centers for Disease Control and Prevention (CDC). Maternal
the reporting provider. Advice garnered from Clinical and infant outcomes among severely ill pregnant and postpar-
Immunization Safety Assessment consultation is to be tum women with 2009 pandemic influenza A (H1N1)—United
used in further decision-making regarding future vac- States, April 2009-August 2010. MMWR Morb Mortal Wkly
Rep 2011;60:1193–6.
cination rather than immediate patient care.
10. Håberg SE, Trogstad L, Gunnes N, Wilcox AJ, Gjessing HJ,
Samuelsen SO, et al. Risk of fetal death after pandemic influ-
CONCLUSION enza virus infection or vaccination. N Engl J Med 2013;368:
333–40.
Vaccination during pregnancy is a vital preventive
11. Louie JK, Acosta M, Jamieson DJ, Honein MA; California
measure in routine obstetric care, serving to protect Pandemic (H1N1) Working Group. Severe 2009 H1N1 influ-
mother, fetus, and infant. Influenza and diphtheria enza in pregnant and postpartum women in California. N Engl
and reduced tetanus toxoids and acellular pertussis J Med 2010;362:27–35.
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Impact of influenza on acute cardiopulmonary hospitaliza-
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for postpartum administration (measles–mumps– 1094–102.
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safe for use during pregnancy but specific studies or 14. Zaman K, Roy E, Arifeen SE, Rahman M, Ragib R, Wilson E,
et al. Effectiveness of maternal influenza immunization in moth-
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