Vaccine 33 (2015) 64366440

Contents lists available at ScienceDirect

Vaccine
journal homepage: www.elsevier.com/locate/vaccine

Maternal benets of immunization during pregnancy

Geeta K. Swamy a, , Richard H. Beigi b
a
Department of Obstetrics and Gynecology, Duke University, Durham, NC, United States
b
Department of Obstetrics, Gynecology and Reproductive Sciences, Magee-Womens Hospital of the University of Pittsburgh Medical Center,
Pittsburgh, PA, United States

a r t i c l e i n f o a b s t r a c t

Article history: The US Centers for Disease Control & Prevention currently recommend routine immunization to prevent
Available online 16 September 2015 17 vaccine-preventable diseases that occur in infants, children, adolescents, or adults. Pregnant women
are at particularly high risk for morbidity and mortality related to several vaccine-preventable diseases.
Keywords: Furthermore, such illnesses are also associated with adverse pregnancy outcomes such as spontaneous
Maternal immunization abortion, congenital anomalies, preterm birth, and low birthweight. In addition to directly preventing
Vaccine
maternal infection, vaccination during pregnancy may offer fetal and infant benet through passive
Passive immunity
immunization. Several vaccines aimed at providing passive immunity to neonates are either currently
recommended or in development. This article specically addresses maternal benets of maternal immu-
nization following (1) vaccines recommended for all pregnant women; (2) vaccines recommended for
pregnant women with particular risk factors; and (3) novel vaccines currently under development that
primarily aim to at reduce infant morbidity and mortality.
2015 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license
(http://creativecommons.org/licenses/by/4.0/).

1. Introduction pregnancy [4]. In addition to the six vaccines (vaccines against

Pregnancy is a particularly susceptible period for maternal and
infant complications associated with vaccine preventable diseases
(VPDs). Pregnant women are at high risk for inuenza-related
morbidity and mortality, including higher rates of hospitalization,
cardiopulmonary complications, and death compared to the gen-
eral public [1]. Maternal inuenza infection is associated with
adverse birth outcomes including preterm birth, fetal growth
restriction, and fetal demise [1]. Both maternal and fetal compli-
cations are further elevated during pandemic inuenza seasons.
Maternalfetal transmission of varicella and rubella are associated
with congenital malformations and life-long infection in the case of
hepatitis B. Beyond preventing maternal and fetal infection, mater-
nal immunization should provide infant protection through passive
immunization, i.e. via transplacental transfer of maternal IgG anti-
bodies as well as transfer of maternal IgA antibodies via breast
milk [2,3]. The potential for passive immunization to protect young
infants against pertussis infection has been the primary driver for
the recent recommendation for administration of tetanus, diphthe-
ria, acellular pertussis (Tdap) vaccination during each and every
Corresponding author at: Duke University, 2608 Erwin Rd, Suite 210 Durham,
NC 27705, United States. Tel.: +1 919 668 1600; fax: +1 919 613 1550.
E-mail address: geeta.swamy@duke.edu (G.K. Swamy).
inuenza, Tdap, pneumococcus, meningococcus, Hepatitis A and
B) that are currently recommended by the US Centers for Dis-
ease Control & Prevention (CDC) for use during pregnancy (with
some contingent upon risk factors), novel vaccines against group B
streptococcus and respiratory syncytial virus are currently being
evaluated for administration during pregnancy [57]. Although
novel vaccine candidates are focusing primarily on the potential
for infant disease prevention, this article specically addresses
maternal benets of immunization during pregnancy following:
(1) vaccines recommended for all pregnant women; (2) vaccines
recommended for pregnant women with particular risk factors;
and (3) vaccines primarily aimed at reducing infant morbidity and
mortality (Table 1).
2. Vaccines recommended for all pregnant Women
2.1. Inuenza
Approximately 20% of the US population will have inuenza dur-
ing a single non-pandemic season compared to nearly 50% during a
pandemic season [1]. Similarly, 20% of pregnant women will suffer
from an inuenza-like illness (ILI) during a non-pandemic season,
with 10% having laboratory-conrmed inuenza [8]. Presumably
due to changes in immunology and cardiorespiratory physiology
rather than susceptibility to acquisition, pregnant and immediately

http://dx.doi.org/10.1016/j.vaccine.2015.08.035
0264-410X/ 2015 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
 G.K. Swamy, R.H. Beigi / Vaccine 33 (2015) 64366440
Table 1
Licensed and novel vaccines for pregnant women.
Vaccines recommended for all pregnant Vaccines recommended for pregnant women with risk factors
women
Inactivated inuenza vaccine (IIV) Pneumococcal polysaccharide 23-serotype vaccine (PPSV23)
Tetanus, diphtheria, acellular pertussis (Tdap) Meninogococcal tetravalent polysaccharide vaccine (MPSV4)
Inactivated hepatitis A vaccine
Recombinant hepatitis B vaccine
postpartum women are at high risk for inuenza-related morbidity
and mortality including hospitalization, cardiopulmonary compli-
cations, and death [9]. Beyond maternal complications, inuenza
infection in pregnancy is associated with adverse birth outcomes
including spontaneous abortion, preterm birth, low birthweight,
and fetal demise [1]. Both maternal and fetal complications increase
even further during pandemic seasons [10,11].
Based on the potential for maternal morbidity and mortal-
ity associated with inuenza during pregnancy, the CDC and
the American College of Obstetrics & Gynecology (ACOG) recom-
mend inactivated inuenza vaccine (IIV) for all women who will
be pregnant during inuenza season [12]. Initial recommenda-
tions for IIV administration during pregnancy made in 1997 were
extrapolated from the documented efcacy and safety of IIV in non-
pregnant adults. Until the 2009 pandemic, there were only a few
small-scale studies on the safety and immunogenicity of mater-
nal inuenza vaccination. In a randomized trial of 340 pregnant
women in Bangladesh, Zaman et al. demonstrated a 36% reduction
in laboratory-conrmed inuenza among women who received IIV
during the third trimester compared to women who received pneu-
mococcal vaccine [2]. While this study was potentially limited by
the lack of a placebo control group, Madhi et al. recently com-
pleted a randomized trial of IIV vs. placebo in 2000 pregnant
women in South Africa [13]. With inuenza attack rates of 3.6% vs.
1.8% among HIV uninfected placebo and IIV groups respectively,
IIV vaccine efcacy in this pregnant population was 50.4% (95%
CI 14.571.2). For women with HIV infection, vaccine efcacy was
57.7% (95% CI 0.282.1) with attack rates of 17% vs. 7% for placebo
and IIV groups, respectively. Black et al. were unable to demonstrate
vaccine effectiveness against hospital admissions and physician
outpatient visits due to respiratory illness among pregnant women
cared for in a health system level analysis over ve consecutive
non-pandemic seasons [14]. The lack of demonstrated effectiveness
may be due to the use of respiratory illness rather than laboratory
conrmed inuenza and that hospitalizations among the entire
population of pregnant women were uncommon, regardless of
vaccination status. However, a population-based study of 117,347
Norwegian women who were pregnant during the 20092010 pan-
demic revealed a 70% reduction in clinical diagnosis of inuenza,
suggesting that vaccine efcacy during a novel pandemic season
may offer even greater maternal benet than seasonal vaccination
[15].
Successful public health promotion by the CDC and ACOG led
to inuenza vaccine coverage exceeding 50% for the rst time
in 20122013 [16]. Studies assessing vaccine acceptance have
clearly identied a lack of knowledge of recommendations, lack
of obstetric provider recommendation, and lack or misunderstand-
ing of safety data during pregnancy as the key factors inuencing
inuenza vaccine uptake during pregnancy [17,18]. Thus, con-
tinued research on inuenza vaccination during pregnancy and
education of obstetric providers and pregnant women is warranted.
With approximately 4 million births in the US annually, maternal
inuenza immunization has great potential to improve maternal
health during pregnancy and the immediate postpartum period
when the risks of inuenza are greatest.
6437
Novel vaccines aimed at reducing infant infection
through maternal immunization
Trivalent group B streptococcus polysaccharide
vaccine
Inactivated respiratory syncytial virus vaccine
2.2. Tetanus, diphtheria, and pertussis
Childhood vaccination combined with decennial booster and
exposure-related dosing against tetanus and diphtheria has led to
the near eradication of both diseases in the US. Pertussis or whoop-
ing cough, however, has been on the rise for the last two to three
decades following a long period of active disease control and pre-
vention. Although the incidence of pertussis has increased across
the entire population, disease-related morbidity and mortality pri-
marily affects infants [19]. Infants are most commonly exposed to
pertussis through close contact, with 4760% of cases due to expo-
sure from infected parents [20]. Furthermore, adults with pertussis
are often unaware of their diagnosis, given that many adults are
either asymptomatic or have symptoms of a common cold.
Vaccination efforts to reduce the incidence of pertussis among
young infants have previously focused on cocooning, or strate-
gies to immunize close contacts of young infants against pertussis.
The initial strategy including immediate postpartum maternal
vaccination combined with antenatal vaccination among previ-
ously non-vaccinated pregnant women failed to affect the ongoing
pertussis outbreaks. In October 2012, the CDC changed its rec-
ommendation on vaccination during pregnancy, now advising
obstetric providers to administer Tdap during each pregnancy,
regardless of prior Tdap receipt [4]. This strategy is based on
the concept of passive immunization in which maternally-derived
vaccine-induced antibodies cross the placenta into the fetal cir-
culation. Passive immunization can protect young infants during
the rst few months of life when they are most vulnerable to per-
tussis and prior to establishing immunity from their own primary
vaccination series [20,21].
While it is imperative that we continue efforts to reduce the
incidence of infant pertussis, many questions remain regarding
the potential benets and/or risks of Tdap administration during
pregnancy, including the potential effect of repeated close-interval
dosing among women having more than one pregnancy in a rel-
atively short period of time, e.g. 13 years, and whether repeated
doses of Tdap actually continues to boost pertussis antibody levels
in pregnant women. Although relatively small with 48 pregnant
and 32 non-pregnant, Tdap nave women, Munoz et al. demon-
strated that Tdap administration during pregnancy is immunogenic
and safe [22]. However, the overall lack of data on the potential
maternal benet of Tdap vaccination, i.e., to prevent pertussis in
pregnant women themselves, as well as the lack of both immuno-
genicity and safety data following repeated Tdap administration,
represents a signicant knowledge gap. Ongoing larger-scale stud-
ies of Tdap during pregnancy will provide much needed data in the
near future [23,24].
3. Vaccines recommended for all pregnant women with
risk factors
3.1. Pneumococcal disease
Pneumococcal disease, caused by the Gram-positive Strep-
tococcus pneumoniae bacterium, is associated with substantial
6438 G.K. Swamy, R.H. Beigi / Vaccine 33 (2015) 64366440
morbidity and mortality resulting from pneumonia, bacteremia,
and meningitis [25]. Pneumococcal pneumonia, the most common
manifestation, affects 900,000 Americans and results in 400,000
hospitalizations and 57% mortality each year. Less common pre-
sentations include bacteremia and meningitis, which affect about
12,000 and 3000 individuals each year, respectively, with 1015%
mortality. Although the incidence of pneumonia during pregnancy
is fairly low, the disease course is similar to that of inuenza, likely
attributable to the same pregnancy-associated physiologic respira-
tory changes and alterations in cell-mediated immunity, resulting
in higher rates of hospitalization, acute respiratory distress syn-
drome (ARDS), cardiorespiratory failure, and death [26]. Obstetric
complications include fetal distress, preterm birth, and low birth-
weight [26].
Current CDC guidelines recommend the 23-serotype polysac-
charide vaccine (PPSV23) for children and adults with chronic
medical conditions and other risk factors including chronic heart
or lung disease (asthma, diabetes, cigarette smoking), alco-
holism, chronic liver disease, cerebrospinal uid leaks, cochlear
implants, congenital or acquired immunodeciencies, diseases
requiring immunosuppressant therapy, sickle cell disease and
other hemoglobinopathies, and functional or anatomic asplenia
[27]. In addition, the 13-serotype pneumococcal conjugate vaccine
(PCV13) is recommended for all children and additional high risk
adult subpopulations [28]. While currently available data do not
support the need for widespread use of PCV13 or PPSV23 during
pregnancy [29], a systematic review of observational studies and a
randomized trial of PPSV23 given during pregnancy demonstrated
no maternal or fetal safety concerns [22,30]. Furthermore, maternal
PPSV23 vaccination provides protective antibody levels for at least
one year following delivery and higher neonatal antibody levels. A
recent Cochrane review found insufcient evidence to suggest that
maternal vaccination could reduce infant pneumococcal infection
via passive immunization [31]. Nevertheless, in accordance with
CDC guidelines for adult immunization, PPSV23 should be given to
pregnant women for their own benet with additional risk factors
as described above.
3.2. Meningococcal disease
Neisseria meningitidis causes rare, but often deadly, meningi-
tis and sepsis in about 1000 people in the US each year [32].
Although susceptible to antibiotics, meningococcal disease carries
a mortality rate of 1015% and a 20% rate of severe morbidity
among survivors including limb amputations, strokes, and neu-
rocognitive abnormalities. In 2005, the tetravalent meningococcal
conjugate vaccine (MCV4) was included in the US adolescent vacci-
nation schedule, replacing the tetravalent polysaccharide vaccine
(MPSV4) based on a longer duration of vaccine-induced immu-
nity with MCV4. Similar to PPSV23 and PCV13, there are several
adult subgroups who are at high risk for meningococcal infection:
those in close living conditions such as dormitories or military bar-
racks, those with complement deciencies, functional or anatomic
asplenia, those residing in hyperendemic areas, and laboratory staff
working with N. meningitidis.
Previously unvaccinated pregnant women with risk factors
for meningococcal disease should be vaccinated. Although MCV4
and MPSV4 are both inactivated products which should not
carry any maternal or fetal risk, available data on meningococ-
cal vaccination in pregnancy involves MPSV4 rather than MCV4.
A systematic review of maternal MPSV4 demonstrated no con-
cern for maternal or fetal complications [30]. ODempsey et al.
demonstrated an adequate maternal antibody response follow-
ing MPSV4 vaccination in the third trimester [33]. Given the
lack of available safety data on MCV4, MPSV4 is recommended
for use during pregnancy based on risk factors described
above [29].
3.3. Hepatitis A
Although generally self-limiting, hepatitis A virus (HAV) causes
fever, vomiting, and jaundice due to acute liver infection. As HAV
is transmitted via fecal-oral contamination from close contact with
infected individuals or contaminated food or drinks, the general
public is at risk for HAV infection [34]. Widespread vaccination
against HAV in the US began in 1999 and has led to a signi-
cant drop in documented cases of HAV in the US [35]. Although
HAV vaccination is currently included in the CDC recommended
childhood immunization schedule, vaccination against HAV is also
recommended for people with high risk for HAV exposure: those
traveling to endemic areas, men who have sex with men, those
in close contact with individuals with HAV infection or receipt
of clotting-factor concentrates, and laboratory or healthcare staff
working with biological specimens. Consistent with CDC guide-
lines, pregnant women with identiable risk factors should receive
HAV vaccine [34]. Although the data on HAV vaccine safety during
pregnancy is lacking, the current inactivated HAV vaccine does not
contain live virus components and is exceedingly unlikely to carry
any risk of maternal or fetal harm.
3.4. Hepatitis B
Associated with acute liver inammation, vomiting, and jaun-
dice, hepatitis B virus (HBV) can either be self-limiting or lead to
a chronic carrier state with long-term morbidity (cirrhosis, liver
cancer, liver failure) and mortality. Individuals with close contact
with an HBV-infected individuals blood and bodily uids are at risk
for disease. The three-dose recombinant DNA HBV vaccine series
provides indenite immunity in most individuals (>90%) and is
currently initiated at birth as part of the CDC recommended child-
hood immunization schedule [36]. Vaccination against HBV has
been proven to be effective given the greater than 60% reduction in
reported cases of HBV over the last 1520 years [35].
Much of the attention on HBV during pregnancy focuses on
the risk of perinatal transmission following primary or chronic
maternal infection, particularly given the high risk of chronic dis-
ease development following perinatal acquisition. As part of that
focus, pregnant women are routinely screened for HBV via surface
antigen (HBsAg) testing followed by neonatal treatment with HB
immunoglobulin (HBIg) prophylaxis and HBV vaccination during
the rst hours of life for infants born to HBV infected mothers [37].
However, unvaccinated pregnant women with risk factors for HBV
acquisition should be counseled on the extremely high effective-
ness of HBV vaccination to prevent maternal and subsequent fetal
infection. Individuals at high risk of HBV acquisition include those
with one or more sexual partner in the past six months, household
or sexual contact with an HBV-infected individual, or intravenous
drug use [36]. Although extensive safety data are limited, HBV
vaccination during pregnancy has not been associated with any
maternal or fetal complications [30]. Therefore, the three-dose HBV
vaccine series should be initiated for previously unvaccinated or
incompletely vaccinated pregnant women with risk factors for HBV
infection.
4. Novel vaccines aimed at reducing infant infection
through maternal immunization
Similar to the recommendation for Tdap to be administered dur-
ing pregnancy, additional vaccines focused on prevention of group
 G.K. Swamy, R.H. Beigi / Vaccine 33 (2015) 64366440
B streptococcus (GBS) and respiratory syncytial virus (RSV) during
early infancy are in development.
4.1. Group B Streptococcus
GBS is leading cause of invasive infection within the rst three
months of life, resulting most commonly in sepsis and meningitis
[38]. Intrapartum antibiotic prophylaxis has signicantly reduced
the incidence of early-onset neonatal GBS (within the rst seven
days of life) in the US. However, there has been no change in
the rates of late-onset GBS disease (from one week to three
months of age), which occurs in 0.290.47 per 1000 live births and
can be equally devastating. Furthermore, strategies of screening
plus intrapartum antibiotic prophylaxis are often impractical in
low-resources settings. Based on available evidence of neonatal
protection against GBS disease in the setting of passive immu-
nity [39], a vaccine against GBS could have a signicant impact on
preventing both early- and late-onset disease.
Albeit the primary objective of a GBS vaccine will be to
reduce infant infection, it is highly plausible that a GBS vaccine
would have signicant benets for maternal health and ultimately
overall pregnancy outcomes. In addition to asymptomatic cervico-
vaginal colonization, GBS causes numerous maternal infections
[40]. Although most GBS urinary tract infections are asymptomatic,
GBS causes about 10% of acute pyelonephritis in pregnancy, which
is highly concerning given the association of pyelonephritis with
adverse pregnancy outcomes (preterm birth, low birthweight, fetal
demise) [41]. Intra-amniotic infection (IAI) is caused by the ascend-
ing spread of vaginal ora, with GBS detected in the amniotic uid
of 15% of cases. Maternal consequences of IAI include serious mater-
nal pelvic infections, sepsis, and postpartum hemorrhage. Maternal
bacteremia occurs in 26% of IAI cases overall and in up to 35%
of cases with conrmed GBS-related puerperal infection IAI and
postpartum endometritis. While septic shock is rare, GBS sepsis
follows bacteremia in 525% of cases [42].
A trivalent conjugated GBS vaccine is being evaluated in phase II
and III studies in pregnant women, with a focus on third trimester
administration to theoretically maximize passive immunity at the
height of antibody transfer rates [6,43]. Although the morbidity
of maternal GBS infection is certainly less than that in the young
infant, maternal disease occurs more frequently and endangers
both mother and infant. Evaluation of the efcacy of the vaccine
to prevent maternal GBS infection as well as optimal timing of
administration to benet both mother and infant will be crucial.
4.2. Respiratory syncytial virus
In the rst year of life, RSV is the leading source of bronchioli-
tis and pneumonia, and frequently results in hospitalization and
recurrent wheezing or asthma. Sixty percent of infants in the US
will suffer from the infection during their rst winterspring RSV
season [44]. While RSV has evaded effective vaccine development
in the past and even been associated with enhanced childhood dis-
ease in the setting of formalin-inactivation [45], numerous vaccine
candidates are in development with target populations ranging
from neonates to the elderly. A recombinant RSV vaccine is cur-
rently under evaluation in a phase II trial of pregnant women with
the goal of providing neonatal protection [5]. The effectiveness of
passive immunization to prevent RSV infection in young infants
is supported by higher RSV cord blood antibody titers resulting in
lower rates of serologic infant infection [46].
There is a paucity of data available on the incidence and impact
of maternal RSV infection during pregnancy. A recent study by
Falsey et al. identied the signicant contribution of RSV to acute
respiratory infection outside of childhood, with a 410% incidence
among high-risk and elderly adults annually. Among the 85% of
6439
symptomatic individuals, 16% required hospitalization with 4%
mortality and disease burden estimates similar to inuenza [47].
We recently published a series of three cases of RSV infection during
pregnancy, two of which required maternal mechanical ventila-
tion and critical care due to severe respiratory compromise [48].
Given the similarities with inuenza, it is very possible that the
incidence and associated complications of maternal RSV infection
have been underestimated. If this is in fact the case, the potential
for a combined maternal and infant benet of an efcacious RSV
vaccine could be great.
5. Summary
Pregnant women have unique and heightened susceptibilities
to greater morbidity and mortality from a variety of bacterial
and viral vaccine-preventable diseases. Currently signicant atten-
tion is focused on developing vaccines for use during pregnancy
with the primary goal of preventing infections in young infants.
While this approach holds tremendous potential for sizable disease
prevention in infants, pregnant women also have signicant oppor-
tunity for disease prevention from both currently recommended
and future vaccines. Maternal-child health can and will continue to
be improved with ongoing efforts to prevent numerous infectious
diseases in both mothers and infants.
Conict of interest
The authors declare no conicts of interest to report.
Funding
Dr. Swamy has received support from GlaxoSmithKline Inc.,
Novartis Vaccine Inc., and Novavax to conduct research funding
for clinical trials in immunization. Dr. Beigi has received research
funding for clinical trials in immunization from Novartis Vaccines
Inc., Novavax, and Genocea BioSciences.
References
[1] Beigi RH. Prevention and management of inuenza in pregnancy. Obstet
Gynecol Clin North Am 2014;41(December (4)):53546.
[2] Zaman K, Roy E, Arifeen SE, Rahman M, Raqib R, Wilson E, et al, et al. Effective-
ness of maternal inuenza immunization in mothers and infants. New Engl J
Med 2008;359(October (15)):155564.
[3] Englund JA, Mbawuike IN, Hammill H, Holleman MC, Baxter BD, Glezen WP.
Maternal immunization with inuenza or tetanus toxoid vaccine for pas-
sive antibody protection in young infants. J Infect Dis 1993;168(September
(3)):64756.
[4] Centers for Disease Control and, Prevention. Updated recommendations for use
of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine
(Tdap) in pregnant women. Advisory Committee on Immunization Practices
(ACIP); 2012. p. 1315.
[5] RSV F vaccine maternal immunization study in healthy third-trimester
pregnant women; 2015. https://clinicaltrials.gov/ct2/show/NCT02247726
[accessed 10.05.15].
[6] Safety and immunogenicity of a trivalent group B Streptococcus vac-
cine in healthy pregnant women; 2015. https://clinicaltrials.gov/ct2/show/
NCT02046148 [accessed 2.05.15].
[7] Centers for Disease Control and Prevention. Adult immunization schedules;
2015. http://www.cdc.gov/vaccines/schedules/hcp/adult.html [accessed 11.05
2015].
[8] Cantu J, Tita AT. Management of inuenza in pregnancy. Am J Perinatol
2013;30(2):99103.
[9] Neuzil KM, Reed GW, Mitchel EF, Simonsen L, Grifn MR. Impact of inuenza on
acute cardiopulmonary hospitalizations in pregnant women. Am J Epidemiol
1998;148(December (11)):1094102.
[10] Pierce M, Kurinczuk JJ, Spark P, Brocklehurst P, Knight M. Ukoss perinatal out-
comes after maternal 2009/H1N1 infection: national cohort study. Br Med J
2011;342:d3214.
[11] Yates L, Pierce M, Stephens S, Mill AC, Spark P, Kurinczuk JJ, et al. Inuenza
A/H1N1v in pregnancy: an investigation of the characteristics and management
of affected women and the relationship to pregnancy outcomes for mother and
infant. Health Technol Assess 2010;34:10982.
6440 G.K. Swamy, R.H. Beigi / Vaccine 33 (2015) 64366440
[12] American College of Obstetricians Gynecologists. Committee opinion no. 608
inuenza vaccination during pregnancy. Obstet Gynecol 2014;124(3):64851.
[13] Madhi SA, Cutland CL, Kuwanda L, Weinberg A, Hugo A, Jones S, et al. Inuenza
vaccination of pregnant women and protection of their infants. New Engl J Med
2014;371(September (10)):91831.
[14] Black SB, Shineeld HR, France EK, Fireman BH, Platt ST, Shay D, et al. Effective-
ness of inuenza vaccine during pregnancy in preventing hospitalizations and
outpatient visits for respiratory illness in pregnant women and their infants.
Am J Perinatol 2004;21(August (6)):3339.
[15] Haberg SE, Trogstad L, Gunnes N, Wilcox AJ, Gjessing HK, Samuelsen SO, et al.
Risk of fetal death after pandemic inuenza virus infection or vaccination. New
Engl J Med 2013;368(January (4)):33340.
[16] Centers for Disease Control Prevention. Inuenza vaccination coverage among
pregnant women United States, 201213 inuenza season. Morb Mortal Wkl
Rep 2013;62(September (38)):78792.
[17] Halperin BA, MacKinnon-Cameron D, McNeil S, Kalil J, Halperin SA. Maintaining
the momentum: key factors inuencing acceptance of inuenza vaccina-
tion among pregnant women following the H1N1 pandemic. Hum Vaccine
Immunother 2014;10(12):362941.
[18] Yudin MH. Risk management of seasonal inuenza during pregnancy: current
perspectives. Int J Women Health 2014;6:6819.
[19] Vitek CR, Pascual FB, Baughman AL, Murphy TV. Increase in deaths from per-
tussis among young infants in the United States in the 1990s. Pediatr Infect Dis
J 2003;22(July (7)):62834.
[20] Edwards KM. Overview of pertussis: focus on epidemiology, sources of infec-
tion, and long term protection after infant vaccination. Pediatr Infect Dis J
2005;24(June (Suppl. 6)):S1048.
[21] Tanaka MVC, Pascual F, Bisgard KM, Tate JE, Murphy TV. Trends in per-
tussis among infants in the United States, 19801999. J Am Med Assoc
2003;290(22):296875.
[22] Munoz FM, Bond NH, Maccato M, Pinell P, Hammill HA, Swamy GK, et al.
Safety and immunogenicity of tetanus diphtheria and acellular pertussis (Tdap)
immunization during pregnancy in mothers and infants: a randomized clinical
trial. J Am Med Assoc 2014;311(May (17)):17609.
[23] Pertussis maternal immunization study, https://clinicaltrials.gov/ct2/show/
NCT00553228 [accessed 31.07.15].
[24] Safety in pregnant women (Tdap), https://clinicaltrials.gov/ct2/show/
NCT02209623 [accessed 31.07.15].
[25] Centers for Disease Control Prevention. Pneumococcal disease; 2015,
http://www.cdc.gov/pneumococcal/index.html [accessed May 2].
[26] Laibl VR, Shefeld JS. Inuenza and pneumonia in pregnancy. Clin Perinat
2005;32(September (3)):72738.
[27] Centers for Disease Control Prevention. Updated recommendations for pre-
vention of invasive pneumococcal disease among adults using the 23-valent
pneumococcal polysaccharide vaccine (PPSV23). Morbid Mortal Wkl Rep
2010;59(September (34)):11026.
[28] Centers for Disease Control Prevention. Use of 13-valent pneumococcal
conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine for
adults with immunocompromising conditions: recommendations of the Advi-
sory Committee on Immunization Practices (ACIP). Morbid Mortal Wkl Rep
2012;61(October (40)):8169.
[29] Centers for Disease Control Prevention. Guidelines for vaccinating pregnant
women; 2015, http://www.cdc.gov/vaccines/pubs/preg-guide.htm#ppsv23
[accessed May 10].
[30] Makris MC, Polyzos KA, Mavros MN, Athanasiou S, Rafailidis PI, Falagas
ME. Safety of hepatitis B, pneumococcal polysaccharide and meningococcal
polysaccharide vaccines in pregnancy: a systematic review. Drug Saf Int J Med
Toxicol Drug Exp 2012;35(January (1)):114.
[31] Chaithongwongwatthana S, Yamasmit W, Limpongsanurak S, Lumbiganon P,
Tolosa JE. Pneumococcal vaccination during pregnancy for preventing infant
infection. Cochrane Database Syst Rev 2015;1:CD004903.
[32] Cohn AC, MacNeil JR, Clark TA, Ortega-Sanchez IR, Briere EZ, Meissner HC,
et al. Prevention and control of meningococcal disease: recommendations of
the Advisory Committee on Immunization Practices (ACIP). Recomm Rep Morb
Mortal Wkl Rep 2013;62(March (RR-2)):128.
[33] ODempsey TJ, McArdle T, Ceesay SJ, Secka O, Demba E, Banya WA, et al.
Meningococcal antibody titres in infants of women immunised with meningo-
coccal polysaccharide vaccine during pregnancy. Arch Dis Child Fetal Neonatal
Ed 1996;74(January (1)):F436.
[34] Fiore AE, Wasley A, Bell BP. Prevention of hepatitis A through active or passive
immunization: recommendations of the Advisory Committee on Immunization
Practices (ACIP). Recomm Rep Morb Mortal Wkl Rep 2006;55(May (RR-
7)):123.
[35] Centers for Disease Control Prevention. Surveillance for viral hepati-
tis United States 2013; 2015, http://www.cdc.gov/hepatitis/Statistics/
2013Surveillance/index.htm [accessed 10.05.15].
[36] Mast EE, Weinbaum CM, Fiore AE, Alter MJ, Bell BP, Finelli L, et al. A compre-
hensive immunization strategy to eliminate transmission of hepatitis B virus
infection in the United States: recommendations of the Advisory Committee
on Immunization Practices (ACIP) Part II: immunization of adults. Recomm Rep
Morb Mortal Wkl Rep 2006;55(December (RR-16)):133, quiz CE31-34.
[37] American College of Obstetricians Gynecologists. ACOG practice bulletin
no. 86 viral hepatitis in pregnancy. Obstet Gynecol 2007;110(October (4)):
94156.
[38] Centers for Disease Control and Prevention. Group B Strep infection
in newborns; 2015, http://www.cdc.gov/groupbstrep/clinical-overview.html
[accessed May 2].
[39] Baker CJ, Kasper DL. Correlation of maternal antibody deciency with sus-
ceptibility to neonatal group B streptococcal infection. New Engl J Med
1976;294(April (14)):7536.
[40] Muller AE, Oostvogel PM, Steegers EA, Dorr PJ. Morbidity related to
maternal group B streptococcal infections. Acta Obstet Gynecol Scand
2006;85(9):102737.
[41] Hill JB, Shefeld JS, McIntire DD, Wendel Jr GD. Acute pyelonephritis in preg-
nancy. Obstet Gynecol 2005;105(January (1)):1823.
[42] Gibbs RS, Schrag S, Schuchat A. Perinatal infections due to group B streptococci.
Obstet Gynecol 2004;104(November (5 Pt 1)):106276.
[43] Immune response induced by a vaccine against group, B., Strepto-
coccus and safety in pregnant women and their, offsprings., 2015;,
https://clinicaltrials.gov/show/NCT01446289. [Accessed 2.05.15].
[44] Centers for Disease Control Prevention. RSV trends and surveillance; 2015,
http://www.cdc.gov/rsv/research/us-surveillance.html [accessed 11.05.15].
[45] Kim HW, Canchola JG, Brandt CD, Pyles G, Chanock RM, Jensen K, et al. Respira-
tory syncytial virus disease in infants despite prior administration of antigenic
inactivated vaccine. Am J Epidemiol 1969;89(April (4)):42234.
[46] Chu HY, Steinhoff MC, Magaret A, et al. Respiratory syncytial virus transplacen-
tal antibody transfer and kinetics in mother-infant pairs in Bangladesh. J Infect
Dis 2014;210(November (10)):15829.
[47] Falsey AR, Hennessey PA, Formica MA, Cox C, Walsh EE. Respiratory syncytial
virus infection in elderly and high-risk adults. New Engl J Med 2005;352(April
(17)):174959.
[48] Wheeler SMD-KS, Heine RP, Grotegut CA, Swamy GK. The maternal impact of
respiratory syncytial virus during pregnancy. Emerg Infect Dis 2015, June;23.
In press, accepted for publication.