Immunizations during pregnancy

INTRODUCTION — Maternal immunization protects both the mother and fetus from the morbidity of certain infections. It can also provide the infant passive protection against vaccine-preventable infections acquired independently after birth [1]. Ideally, immunizations are given prior to conception, but administration during pregnancy is indicated in some situations.

Immunizations to give and avoid during pregnancy and postpartum are discussed in this topic. Other aspects of prenatal care are discussed elsewhere. (See "Prenatal care: Initial assessment" and "Prenatal care: Second and third trimesters".)

GENERAL PRINCIPLES

Overview of immunization — Ideally, individuals should be vaccinated against preventable diseases in their environment prior to conception according to the recommended adult immunization schedule (figure 1 and figure 2) (see 'Preconception immunization' below). Vaccination during pregnancy is warranted when the risk of exposure is high, the infection poses risks to the mother and/or fetus, and the vaccine is unlikely to cause harm. Vaccines appropriate for immunization before, during, and after pregnancy are shown in the table (table 1). Despite maternal immunologic adaptations to pregnancy, immunization of pregnant patients appears to be as effective as in nonpregnant patients [2].

The Infectious Diseases Society of America and the American College of Obstetricians and Gynecologists have each published general guidelines for immunization of pregnant patients [3-6]:

●Providers should be aware of immunizations that are routinely recommended for all pregnant patients: tetanus, reduced diphtheria toxoid, acellular pertussis (Tdap) vaccine and influenza vaccine. These immunizations have a good safety profile in pregnancy, can provide passive protection to the newborn, and are not associated with miscarriage. (See 'Routine prenatal immunizations' below.)

●Providers should administer appropriate non-live vaccines to pregnant patients with medical or exposure indications that put them at risk for vaccine preventable infections. (See 'Immunizations for special circumstances' below.)

●Following delivery, postpartum patients should receive all recommended vaccines that could not be or were not administered during pregnancy (eg, measles, mumps, and rubella; varicella; tetanus toxoid, reduced diphtheria toxoid, Tdap, and human papillomavirus). (See 'Postpartum immunization' below.)

●Providers should be aware of and follow contraindications and precautions for immunization of pregnant patients (eg, avoid administration of live attenuated virus vaccines). (See 'Immunizations to avoid during pregnancy' below.)

Obstetrician-gynecologists (OB/GYN) are often the primary clinicians for females of childbearing age; as such, they are in a good position to screen for immunization status and to provide appropriate vaccinations. However, financial factors (eg, inadequate reimbursement, cost of storing vaccines) and knowledge about vaccine counseling, safety, and administration appear to be barriers to vaccine administration in OB/GYN offices [7,8].

The specific immunization guidelines in this review are based upon recommendations for residents of the United States by the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC). ACIP statements may be viewed and downloaded from the CDC's website. The CDC also has an Immunization Hotline (1-800-232-2522).

Immunogenicity and placental transfer — Healthy pregnant patients can mount a similar immune response to vaccines as healthy nonpregnant patients [9]. Transplacental passage of antibodies depends on maternal concentration, antibody type (significant amounts of IgG are transported but not IgM, IgA, or IgE), IgG subtype (IgG1 is preferentially transported), and gestational age. Fetal IgG concentration is much lower than maternal concentration in the first half of pregnancy, but increases to 50 percent of maternal levels at 28 to 32 weeks of gestation, equals maternal levels by 36 weeks, and often exceeds maternal levels at term [10].

Because maternal IgG levels reach their peak about four weeks after immunization, the gestational age at maternal immunization is an important factor when passive neonatal immunity is a goal (eg, pertussis vaccine). In these cases, the ideal timing of vaccination is in the early third trimester to achieve maximum maternal antibody levels and maximum antibody transfer before delivery. Unlike the pertussis vaccine, the influenza vaccine is given for both maternal and infant protection, and therefore should be provided seasonally to all pregnant patients regardless of gestational age.

Minimizing risks of infection exposure — Pregnant patients should minimize their risk of exposure to infections to which they are susceptible by avoiding travel to high-risk areas (eg, where yellow fever is prevalent), assuring that household members are immunized according to standard immunization schedules, and maintaining good hygienic practices (eg, hand washing, consuming clean water, and cooking food adequately).

SAFETY

Vaccine safety by type — When immunization is performed during pregnancy, the benefits to both mother and fetus should outweigh the risks. There is no evidence of harm to pregnant patients or fetuses from administration of inactivated vaccines. However, live vaccines that are considered safe in children and adults may be harmful to a developing fetus (see 'Live vaccines' below). They are generally avoided during pregnancy.

Toxoids, inactivated vaccines, immune globulin preparations — Toxoids, inactivated virus vaccines, immune globulin preparations, and live viral and bacterial vaccines can augment an individual's immune status. All but the live vaccines are generally considered safe for administration to pregnant patients, since there is no evidence that they have harmful effects on the fetus or pregnancy. However, not all vaccines have been specifically studied in pregnancy.

Live vaccines — Live vaccines have the potential for infecting the fetus. Harmful effects have not been reported in newborns of mothers who received live vaccines during pregnancy, although subclinical infection has been documented. Because a risk of fetal damage cannot be definitively excluded, use of live vaccines is strongly discouraged during pregnancy unless the pregnant patient is at substantial risk of exposure to a natural infection associated with serious morbidity or mortality. The risk-benefit ratio of administering live vaccines should be weighed individually for such patients in consultation with an infectious disease expert. As an example, the yellow fever vaccine and the live attenuated oral polio vaccine may be warranted for pregnant patients who have a high risk of imminent exposure. (See 'Yellow fever' below and 'Poliovirus' below.)

If a live virus vaccine is inadvertently given to a pregnant patient, or if a patient becomes pregnant within four weeks after vaccination, they should be counseled about the potential effects on the fetus [11,12]. Termination of pregnancy is not warranted for this indication, given the absence of documented harm [13]. (See 'Immunizations to avoid during pregnancy' below.)

Vaccine safety by trimester — Medically indicated toxoids, inactivated virus vaccines, and immune globulin preparations can be given at any gestational age, even in the first trimester during organogenesis, when special risks to the unimmunized pregnant patient, fetus, or newborn are present. As an example, seasonal influenza vaccine should be administered as soon as it becomes available, regardless of gestational age.

If prompt administration is not medically indicated, it is preferable to delay administration of these agents until the second trimester since the possibility of risk to fetal development cannot be definitively excluded. Waiting until the second trimester also helps to avoid spurious associations in the patient's mind between immunization and common adverse first trimester events (eg, miscarriage, congenital anomalies). Additionally, vaccination between weeks 28 and 32 of gestation may optimize the transfer of antibodies to the fetus [14].

Lack of autism association with immunizations — The overwhelming majority of epidemiologic evidence does not support an association between immunizations and autism. (See "Autism spectrum disorder and chronic disease: No evidence for vaccines or thimerosal as a contributing factor".)

Thimerosal, adjuvants, and vaccine safety

●Thimerosal – Although some vaccines given to adults contain thimerosal (a mercury preservative used in vaccines), there is no evidence that thimerosal-containing vaccines cause adverse effects in offspring of patients who received these vaccines during pregnancy. The Advisory Committee on Immunization Practices does not recommend avoidance of thimerosal-containing vaccines for any group, including pregnant patients [15]. A list of vaccines by brand name and with their thimerosal content is available from the US Food and Drug Administration at http://www.fda.gov/biologicsbloodvaccines/safetyavailability/vaccinesafety/ucm096228.htm.

●Adjuvants – Some vaccines contain adjuvants which are used to help increase an individual's response to a vaccine; a list of the various adjuvants used in vaccines administered in the United States is available online. One such adjuvant, insoluble aluminum salts (eg, aluminum phosphate), is widely used in vaccines administered in pregnancy (eg, Tdap) and has a good safety profile. (See "Standard childhood vaccines: Parental hesitancy or refusal", section on 'Aluminum adjuvants' and 'Tetanus, diphtheria, and pertussis vaccination' below.)

Newer adjuvants (eg, AS01_B, CpG 1018) have been developed to target specific components of the immune response but are generally avoided in pregnancy because of a lack of safety data. (See 'Hepatitis B' below and 'Zoster' below.)  

PRECONCEPTION IMMUNIZATION — Ideally, individuals should be vaccinated against preventable diseases in their environment prior to conception according to the recommended adult immunization schedule. Adult immunization recommendations in the United States developed by the Advisory Committee on Immunization Practices (ACIP) are shown in the tables (figure 1 and figure 2).

Several infections with serious consequences for the mother or fetus can be prevented by preconception vaccination [16]. In particular, for susceptible individuals of childbearing age who may become pregnant, ensuring immunity against measles, mumps, rubella, and varicella is important, since these immunizations are contraindicated during pregnancy and infection in nonimmune pregnant patients can adversely affect pregnancy outcomes.

Before administering a live vaccine to a female of childbearing age, reasonable practices should include asking the patient if they are pregnant or could become pregnant in the next four weeks and counseling them about the potential risks of vaccination during pregnancy or just before conception. Routine pregnancy testing before vaccination is not recommended if absence of pregnancy is reasonably certain by history (table 2).

The ACIP recommends avoiding pregnancy for 28 days following each dose of a live vaccine (for varicella vaccination, the manufacturer recommends waiting three months) [15]. Nevertheless, adverse outcomes in patients who became pregnant soon after receiving these vaccines have not been established [13]. (See 'Measles, mumps, rubella' below and 'Varicella' below and 'Poliovirus' below.)

●Measles, mumps, rubella – Measles-related morbidity appears to be greater in pregnant than in nonpregnant patients, and measles, mumps, and rubella infections are associated with adverse pregnancy outcomes. These are discussed in detail elsewhere. (See "Measles: Clinical manifestations, diagnosis, treatment, and prevention", section on 'Pregnant women' and "Rubella in pregnancy", section on 'Clinical manifestations' and "Mumps".)

•Rubella – Documenting immunity to rubella is a routine component of preconception care. The measles, mumps, rubella (MMR) vaccine, a live attenuated vaccine, should be given to patients who are not pregnant and who do not have evidence of immunity to rubella [17]. For patients in the childbearing age group not at high risk, evidence of immunity includes: documentation of age-appropriate completion of MMR vaccination (at least one dose of live rubella-containing vaccine), laboratory evidence of immunity or laboratory confirmation of disease [17]. However, transmission of infection can occur among individuals who meet criteria for presumptive immunity.

The test of choice for determining rubella immunity is an immunoglobulin G (IgG) antibody titer; an IgM antibody titer is unnecessary unless there is suspicion of recent/acute infection. Once rubella immunity has been documented, repeat rubella serology is unnecessary in subsequent pregnancies. Vaccinated patients of childbearing age who have received one or two doses of rubella-containing vaccine and have rubella serum IgG levels that are not clearly positive should receive one additional dose of MMR vaccine (for a maximum of three doses) and do not need to be retested for serologic evidence of rubella immunity [17]. (See "Measles, mumps, and rubella immunization in adults", section on 'Who should be immunized' and "Measles, mumps, and rubella immunization in adults", section on 'Documenting immunity'.)

•Measles – Documenting immunity to measles has become a component of preconception care, given the rise in incidence of the infection in recent years [18]. For patients in the childbearing age group not at high risk of measles exposure, evidence of immunity includes: documentation of age-appropriate completion of MMR vaccination (at least one dose of live measles-containing vaccine), laboratory evidence of immunity, or laboratory confirmation of measles [17,19]. Adults at high risk of measles exposure (eg, health care workers, students at post-high school institutions, international travelers) should have had at least two doses of a live measles-containing vaccine for evidence of immunity [17].

Any of the standard serologic assays for measles-specific IgG may be used for laboratory documentation of measles immunity. Nonpregnant patients whose vaccination history cannot be obtained and who are nonimmune by serology should receive one or two doses of the MMR vaccine, depending on their risk category. The two-dose series of the MMR vaccine is safe and is 97 percent effective at preventing measles infection. (See "Measles, mumps, and rubella immunization in adults", section on 'Who should be immunized' and "Measles, mumps, and rubella immunization in adults", section on 'Documenting immunity'.)

●Varicella – Varicella-zoster infection during pregnancy can be associated with severe maternal complications and can cause congenital varicella syndrome and neonatal varicella-zoster infection. This is discussed in detail elsewhere. (See "Varicella-zoster virus infection in pregnancy".)

According to the ACIP, nonpregnant patients without evidence of immunity who do not plan to become pregnant within the next month are candidates for immunization with the varicella vaccine, which is given in two doses four to eight weeks apart. We agree with ACIP and American College of Obstetricians and Gynecologists recommendations to avoid pregnancy for one month after receiving the live varicella vaccine [20,21]; the manufacturer labeling recommends waiting three months [22]. Evidence of immunity to varicella in this population includes any of the following [20]:

•Documentation of age-appropriate varicella vaccination

•History of varicella based on diagnosis or verification of varicella by a health care provider

•History of herpes zoster based on health care provider diagnosis

•Laboratory evidence of immunity or laboratory confirmation of disease; or

•Birth in the United States before 1980, except pregnant patients, health care personnel, or immunocompromised patients

ROUTINE PRENATAL IMMUNIZATIONS

Tetanus, diphtheria, and pertussis vaccination — Vaccination with the adjuvanted tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) is routinely recommended during pregnancy [3]. Pregnant patients who have not previously been fully vaccinated against tetanus and diphtheria should also receive a tetanus and diphtheria toxoid (Td) series.

Administration — Available vaccines that protect against tetanus, diphtheria, and pertussis include the tetanus and diphtheria toxoid vaccine (Td) and the tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap). The specific vaccine used depends on the prior immunization status of the pregnant patient [23-25]:

●Td immunization complete – Pregnant patients who have been previously immunized with a full three-dose series of Td vaccine should receive a single dose of Tdap, ideally during the early part of the 27 to 36 week gestational age range [24,26-28]. Tdap is indicated in each pregnancy, even if the patient has a previous history of pertussis or vaccination, and even if consecutive pregnancies occur within 12 months.

For patients for whom 10 years has elapsed since the last Td booster, this Tdap dose in pregnancy will also serve as a booster vaccination against tetanus and diphtheria. If the Tdap cannot be given, a Td booster during pregnancy is recommended if ≥10 years have elapsed since a previous Td booster (administer during the second or third trimester) or if booster protection is needed for wound management (administer when needed). Booster protection for wound management is advised when the last booster was ≥5 years before a wound that is not clean and minor. (See "Tetanus-diphtheria toxoid vaccination in adults", section on 'Immunization for patients with injuries'.)

●No, incomplete, or unknown immunization against tetanus and diphtheria – Pregnant patients who have not received three doses of a vaccine containing tetanus and diphtheria toxoids (Td) should undertake or complete the series of three vaccinations. The preferred schedule in pregnant patients is at time 0, 4 weeks later, and at 6 to 12 months after the initial dose.

To also provide protection against pertussis, at least one of these doses should be with Tdap; ideally, Tdap is given during the early part of the 27 to 36 week gestational age range.

Tdap can be given earlier than 27 to 36 weeks and at any stage of pregnancy if a person lives in an area with a pertussis epidemic or requires a tetanus booster as part of wound management [24]. If it is given early in pregnancy, it should not be repeated later in pregnancy. The rationale for the suggested timing of Tdap vaccination is discussed below. (See 'Rationale, efficacy, and safety' below.)

If Tdap is not administered during pregnancy, it should be administered immediately postpartum to patients who have not previously received Tdap. This can provide protection to the infant indirectly or, if breastfeeding, through transfer of maternal antibodies in breast milk; however, the maternal immune response may not be sufficiently rapid to protect the infant until two weeks post-immunization [26].

Additional information on Tdap and Td can be found separately. (See "Pertussis infection in adolescents and adults: Treatment and prevention" and "Tetanus-diphtheria toxoid vaccination in adults".)

Vaccination of household contacts — Tdap is also recommended for individuals (such as family members and childcare providers) who are expected to have close contact with a newborn or infant younger than 12 months and have not received Tdap previously [23,24]. Pregnant patients are the only population in whom repeated Tdap immunization is recommended; repeated immunization is not recommended for nonpregnant household contacts, for whom a single adult dose of Tdap suffices.

Rationale, efficacy, and safety

●Protection against pertussis – The prevalence of pertussis in the United States has been increasing, in part because pertussis immunity after vaccination or disease wanes over time. Adults who develop pertussis can transmit the disease to susceptible infants in the household, which is a concern because infants under three months of age are at highest risk of morbidity and mortality from this disease [25,29]. Over 50 percent of infants with pertussis contract the disease from family members, mostly from their mothers [30,31]. While the incidence and clinical symptoms of pertussis may be similar in pregnant compared with nonpregnant patients [32], multiple observational studies suggest a decreased risk of infant pertussis with maternal vaccination during pregnancy [33-44]. Vaccination of the mother (and other household contacts) directly protects them, and thus can significantly decrease the risk of infant exposure. Placental transfer (and breast milk transfer in those that are breastfeeding [45]) of maternal antibodies is also highly effective in providing passive protection against pertussis in infants in the first few months of life, as the infant is not eligible for active immunization until six weeks of age. (See 'Immunogenicity and placental transfer' above.)

The Advisory Committee on Immunization Practices (ACIP) recommendation for vaccination between 27 and 36 weeks of gestation (and preferably during the earlier part of this period) is intended to maximize both maternal antibody response and passive antibody transfer to the infant [24,46], based on the following lines of evidence from observational studies:

•Vaccination before or too early in pregnancy may result in suboptimal protection. In a study of women vaccinated remote from delivery (ie, before conception and within two years of delivery or in early pregnancy), cord blood pertussis-specific antibody levels were often insufficient to protect the infant against infection in the first two to three months of life, suggesting rapid waning of maternal antibody levels [47].

•Vaccination too late in pregnancy also likely results in suboptimal protection. In one study, maternal vaccination ≤6 days before birth was associated with lower vaccine effectiveness among infants compared with earlier vaccination [34].

•Among women vaccinated during the third trimester, vaccination from 27 through 30 weeks gestation has been associated with higher neonatal core blood pertussis antibody levels compared with vaccination from 31 through 36 weeks [48,49]. Also, infants of women vaccinated with Tdap in early third trimester (28 to 32 weeks) had higher levels of high avidity pertussis antibodies than those whose mothers were vaccinated in late third trimester (33 to 36 weeks) [50]. High avidity antibodies are expected to confer greater protection to the neonate.

However, not all studies support 27 through 30 weeks gestational age as the optimal time for maternal vaccination. One study of women vaccinated during the third trimester reported similar cord antibody levels with immunization before and after 31 weeks [51]. Another study reported that second trimester immunization (14 to 27 weeks) resulted in higher infant antibody levels than third trimester (≥28 weeks) immunization [52]. The authors estimated 80 percent of infants exposed to second trimester maternal vaccination would be seropositive at three months of age versus 55 percent following third-trimester immunization. A randomized trial should be performed to determine optimal timing of vaccination in pregnant patients.

Passive protection can blunt the infant's immune response to infant doses of diphtheria, tetanus toxoids, and pertussis (DTaP) and routinely administered conjugate vaccines, but this does not appear to reduce vaccine effectiveness [35,39,42,53-55]. In a retrospective study of nearly 150,000 infants, infants exposed in utero to Tdap vaccine were better protected against pertussis during the first year of life than unexposed infants at every level of DTaP vaccine exposure [39].

●Protection against tetanus – Neonatal tetanus is rare in countries where universal immunization of children/adults with tetanus toxoid is routine. Estimated vaccine effectiveness is about 90 percent [34,36]. However, in some resource-limited countries, it is one of the leading causes of neonatal death due to unclean cord cutting and care practices, unhygienic deliveries, and lack of maternal tetanus immunization [56]. This preventable disease can be eliminated by giving tetanus toxoid to pregnant patients who have not been vaccinated or who are inadequately vaccinated, thereby passively immunizing the fetus and neonate [57,58]. Where appropriate, promotion of aseptic obstetric practices, including those involving postnatal umbilical cord care, is also effective in reducing neonatal tetanus [59].

●Safety – Tdap is safe to use during pregnancy [60-64]. A 2017 systematic review of primarily observational studies of Tdap administered to pregnant patients did not identify any increase in significant adverse maternal, infant, or pregnancy outcomes, even among those who had received Tdap or other tetanus-containing vaccine within the previous five years [60].

●Vaccine acceptance – Despite the ACIP recommendations, Tdap vaccination rates in pregnancy remain low in the United States. In a United States Centers for Disease Control and Prevention survey of women pregnant during the 2017-2018 influenza season, only 54 percent of survey respondents reported receiving Tdap during pregnancy [65]. Reasons for not receiving the vaccine included lack of knowledge regarding the need for vaccination during each pregnancy. Patients who were offered the vaccine had a higher vaccination rate than patients who only received a recommendation for immunization.

Inactivated influenza vaccine — All patients who are pregnant or might be pregnant during the influenza season should receive the inactivated influenza vaccine as soon as it becomes available and before onset of influenza activity in the community, regardless of their stage of pregnancy [66,67]. Vaccination after onset of influenza activity is still beneficial as long as influenza viruses are circulating. Inactivated influenza vaccine is administered by intramuscular injection into the deltoid muscle.

Influenza vaccination in pregnant patients, including vaccine administration, efficacy, and safety, is discussed in more detail elsewhere. (See "Seasonal influenza and pregnancy", section on 'Vaccination'.)

IMMUNIZATIONS FOR SPECIAL CIRCUMSTANCES

Pre-exposure prophylaxis — Some pregnant patients are at high risk for acquiring an infection because of comorbidities, occupation, habits, travel plans, area of residence, or exposure risk. Patients who meet vaccine recommendations should be immunized if a vaccine is available and not known or suspected to be harmful in pregnancy, and if infection could result in significant harm to mother or baby. In general, non-live vaccines are not more dangerous to the pregnant patient or their fetus than the disease they are designed to prevent, although each vaccine should be considered individually.

Pneumococcal vaccination — Pneumococcal vaccination is recommended for adults with conditions that increase the risk of invasive pneumococcal disease (table 3) [68]. Ideally, the vaccine should be given prior to conception, but the indications for administration are not altered by pregnancy. (See "Pneumococcal vaccination in adults".)

Pneumococcal vaccine options include pneumococcal conjugate vaccines (PCV-20 and PCV-15) and a pneumococcal polysaccharide vaccine (PPSV23).

●PCV-20 and PCV-15 – Data on the safety of pneumococcal conjugate vaccines during pregnancy are insufficient to inform guidelines [69,70]. In clinical trials, seven patients who received the PCV20 were later found to be pregnant; no adverse outcomes in mothers or infants were noted [71]. Studies of PCV20 in pregnant rabbits also showed no adverse effects [72]. For most patients, delaying administration until the second trimester may be a reasonable approach. However, for patients at very high risk of invasive pneumococcal disease (eg, functional/anatomic asplenia, immunosuppression resulting from chemotherapy or systemic glucocorticoid use), the vaccine should be administered earlier.

●PPSV23 – PPSV23 appears safe when given in the second and third trimesters and may also provide passive immunization to the newborn [73]; however, a reduction in neonatal infection has not been demonstrated [74]. There is little information on its safety during the first trimester of pregnancy though adverse events have not been reported after inadvertent administration [75].

Haemophilus influenzae vaccination — Haemophilus influenzae type b (Hib) conjugate vaccine is an inactivated vaccine recommended for adults who have not received the childhood Hib series and are at increased risk for invasive Hib disease due to certain chronic conditions (eg, sickle cell disease, leukemia, human immunodeficiency virus [HIV] infection, or splenectomy). The indications for administration are not altered by pregnancy, and studies suggest that Hib vaccination during the third trimester is safe and immunogenic [14]. However, administration should be discussed individually, especially since Hib vaccine formulations in the United States include only combination vaccines. (See "Prevention of Haemophilus influenzae type b infection", section on 'High risk of invasive Hib disease'.)

Meningococcal vaccination — Meningococcal vaccination is recommended for adults with conditions or exposures that increase the risk of infection (table 4); in pregnant patients at high risk of meningococcal disease, the benefits of vaccination likely outweigh any potential risks.

There are two classes of meningococcal vaccines: quadrivalent meningococcal conjugate vaccines (MenACWY [eg, Menveo, MenQuadfi]) and meningococcus serogroup B vaccines (MenB [eg, Trumenba, Bexsero]). Indications for each of the two classes of vaccines differ somewhat but are not altered by pregnancy [76,77]. However, confidence in the safety of these vaccines differs by type:

●MenACWY vaccination appears safe for administration during pregnancy, if indicated. A review of 103 Vaccine Adverse Event Reporting System (VAERS) reports of pregnant women who received MenACWY-D noted no unusual or unexpected pattern of maternal, infant, or fetal adverse events after vaccine administration [78]. There were 17 miscarriages (16.5 percent) and one report of a child with aqueductal stenosis and severe ventriculomegaly. The mother of this child had received the vaccine at seven weeks of gestation but had also received other drugs during her pregnancy.

●For the MenB vaccine, the risks and benefits should be weighed individually. The ACIP recommends that MenB vaccine be deferred until after pregnancy, unless the benefits of vaccination during pregnancy are thought to outweigh the uncertain risks [79]. In MenB clinical trials, of the 34 women who reported pregnancy after at least one dose of the MenB vaccine, 4 (12 percent) experienced spontaneous abortion. Data from manufacturer registries on birth outcomes after maternal vaccination are not yet available.

MPSV4 is no longer recommended for meningococcal vaccination in the United States. VAERS reports of exposure to the meningococcal polysaccharide vaccine MPSV4 during pregnancy have not identified adverse effects among either pregnant patients or newborns of mothers vaccinated during pregnancy [76].

Meningococcal vaccination is discussed in more detail separately. (See "Meningococcal vaccination in children and adults".)

Hepatitis B — Hepatitis B vaccine is a recombinant vaccine that poses no known harm to the fetus or newborn and can be given during pregnancy, if indicated. Although childhood immunization is now routine, some pregnant adults have not been immunized. Hepatitis B vaccination during pregnancy is indicated in:

●Pregnant patients who are completing an immunization series begun prior to conception.

●Unvaccinated, uninfected pregnant patients (hepatitis B surface antigen negative) who are at high risk for acquiring hepatitis B virus (HBV) [80]. High-risk characteristics are detailed separately. (See "Hepatitis B virus immunization in adults", section on 'Vaccine administration'.)

If hepatitis B vaccination is indicated during pregnancy, one of the conventional recombinant vaccines (eg, Recombivax HB, Engerix-B) is recommended. A combined hepatitis A virus recombinant hepatitis B virus vaccine is also available and safe for pregnant individuals who have indications for vaccination against both viruses. A newer, adjuvanted recombinant vaccine that has been licensed for use in the United States (Heplisav-B) is not recommended during pregnancy because of paucity of safety data in this setting [46].

Conventional recombinant hepatitis B vaccines are typically given at time zero, one month later, and six months later, but an accelerated schedule appears to be an effective strategy if completion of the entire immunization series during pregnancy is desired. In one study of pregnant women under 25 weeks of gestation at high risk of acquiring HBV (sexually transmitted disease, current injection drug), hepatitis B vaccine was administered at zero, one month, and four months [81]. Eighty-four percent of the patients received the full series and 90 percent seroconverted after the third dose, with no increase in adverse effects.

Prevaccination screening for hepatitis B antibody is not necessary, although screening for hepatitis B surface antigen is a routine prenatal laboratory test because vertical transmission of HBV can usually be prevented by appropriate intervention (passive and active immunization of offspring at birth). (See "Hepatitis viruses and the newborn: Clinical manifestations and treatment".)

Hepatitis A — There are three vaccines to protect against hepatitis A virus (HAV), two HAV vaccines and a combined HAV and recombinant HBV vaccine; all three are inactivated vaccines and can be given during pregnancy. While childhood immunization is now routine, many adults have not been immunized, and susceptible pregnant patients at increased risk for HAV exposure and/or complications are candidates for vaccination [80]. In the United States, the ACIP recommends vaccination during pregnancy for patients with any of the following [82]:

●Planned international travel

●Injection or noninjection substance use

●Occupational risk for infection

●Close contact with an international adoptee or persons experiencing homelessness

●Concern for a severe outcome from HAV infection (eg, personal history of chronic liver disease or HIV)

Pre-vaccination serology to determine pre-existing immunity to HAV is generally not warranted but is reasonable for individuals with a high likelihood of prior HAV exposure. This is discussed in detail elsewhere. (See "Hepatitis A virus infection: Treatment and prevention", section on 'Role of prevaccine serology'.)

Data in pregnancy are limited [83,84]. In one retrospective study of over 600,000 pregnant women, 1140 women (1 percent) received hepatitis A vaccination during pregnancy; vaccination was not associated with adverse pregnancy outcomes (eg, gestational hypertension, gestational diabetes, pre-eclampsia/eclampsia, cesarean delivery, preterm delivery, or low birthweight), except for a possible association with birth of small-for-gestational-age infants, which was likely due to unmeasured confounders [84].

HAV is a common cause of acute hepatitis associated with significant morbidity and occasional mortality (see "Hepatitis A virus infection in adults: Epidemiology, clinical manifestations, and diagnosis"). Acute maternal HAV infection may be associated with preterm delivery [85]. In utero infection has been reported manifesting as meconium peritonitis, fetal ascites, and polyhydramnios [86,87].

If susceptible individuals are exposed to HAV during pregnancy, HAV vaccination and passive immunization with immune globulin are indicated. (See "Hepatitis A virus infection: Treatment and prevention", section on 'Protection following exposure'.)

Yellow fever — Yellow fever is a mosquito-borne viral hemorrhagic fever that occurs in tropical regions of South America and sub-Saharan Africa and has a high case fatality rate. Pregnant patients should avoid travel to these endemic regions, but if travel is unavoidable, yellow fever vaccine is a consideration. International Health Regulations by the World Health Organization allow countries to require proof of yellow fever vaccine from travelers entering their country. Previously, those regulations specified that a dose of the vaccine was valid for 10 years. From July 11, 2016, the certificate of vaccination is valid for the life of the person vaccinated [88]. However, individuals who get the vaccine while pregnant require a booster dose before their next travel due to a lower seroconversion rate after vaccination during pregnancy.

In contrast to other live vaccines, the live attenuated yellow fever vaccine is not contraindicated during pregnancy; however, the risk of yellow fever exposure must be carefully weighed against the risks of the vaccine, which can be serious. If the risk of yellow fever exposure is high, the yellow fever vaccine can be administered in consultation with an infectious disease specialist [89]. In cases where the risk of disease is low but vaccination is an international travel requirement, a medical waiver may be issued.

As in the general population, yellow fever vaccine can cause serious, including fatal, adverse effects in pregnant patients, although these are very rare events (see "Yellow fever: Treatment and prevention", section on 'Adverse effects'). In large series, yellow fever vaccine does not increase the rate of adverse pregnancy outcomes among women with complete follow-up after vaccination [13,89-92]. Fetal infection after vaccination occurs at a low rate, but has not been associated with an increased risk of major congenital anomalies [92-94]. Inadvertent vaccination is not an indication for pregnancy termination. In a series of 304 babies exposed to yellow fever vaccine during the prenatal period, examination revealed major malformations in 3.3 percent, a rate similar to that in the reference population [92]. A study of 441 women inadvertently vaccinated early in their pregnancy did not find an increased risk for fetal death (7.4/1000 in vaccinated women versus 18.5/1000 in unvaccinated women in the general population) [90]. A smaller study had suggested an increased risk for miscarriage in women vaccinated for yellow fever during pregnancy [95].

If available, post-vaccination serologic testing can be performed in pregnant patients to document an appropriate immune response [89]. Healthy people rarely fail to develop neutralizing antibodies following vaccination, but there are conflicting data about the immune response of pregnant patients to yellow fever vaccination [90,96]. The seroconversion rate among patients who receive the vaccine during the third trimester of pregnancy appears to be lower compared with the general population. As an example, in one study in Nigeria, only 39 percent of pregnant women vaccinated in the third trimester seroconverted at two and four weeks, as opposed to 94 percent of the general population [96]. As a result, it is recommended that patients who were pregnant (regardless of trimester) when they received their initial dose of yellow fever vaccine receive one additional dose of the vaccine before the next travel that puts them at risk for yellow fever infection [89]. Such a booster dose is no longer recommended by the United States Centers for Disease Control and Prevention (CDC) for most other travelers.

Pregnant patients who travel to areas endemic for yellow fever without having undergone vaccination should take precautions to reduce the risk of mosquito exposure, including staying in urban settings, avoiding the outdoors at dawn or dusk, wearing protective clothing outside, and using insect repellant containing DEET on exposed surfaces. The CDC and Environmental Protection Agency recommendations for DEET use in pregnant and lactating patients do not differ from those for nonpregnant adults [97]. (See "Yellow fever: Epidemiology, clinical manifestations, and diagnosis".)

Similar to pregnancy, breastfeeding is a precaution against yellow fever vaccine administration. Two serious adverse events have been reported in exclusively breastfed infants whose mothers were vaccinated [89,98].

Nonpregnant patients who receive the yellow fever vaccine should avoid pregnancy for one month following vaccination.

Poliovirus — Poliomyelitis, a systemic viral infection with varying manifestations ranging from asymptomatic disease to paralysis, has been eradicated from most resource-rich regions of the world, but transmission continues in certain countries, including Pakistan, Afghanistan, Nigeria, Somalia, Ethiopia, Cameroon, Equatorial Guinea, Syria, and Iraq. Pregnant patients should avoid travel, if possible, to areas where the disease is present. If travel is not avoidable, they should be immunized. Although two vaccines, the live attenuated oral polio vaccine (OPV) and an inactivated polio vaccine (IPV), exist globally, only the IPV is available in the United States, and in general, the IPV is the one usually recommended in pregnancy.

Pregnant patients at increased risk for infection who require immediate protection should be given IPV according to the schedule for adults. Adverse effects of IPV administration during pregnancy have not been documented in either the mother or fetus.

In the event that pregnant patients in countries outside the United States warrant vaccination with the live OPV (eg, for outbreak control purposes), exposure to OPV in utero does not appear to increase the risk of adverse infant outcomes. Following mass immunization programs in response to poliovirus epidemics in Finland and Israel, during which thousands of pregnant women were administered OPV, observed rates of growth restriction, perinatal death, preterm birth, and congenital anomalies were not higher than expected [99-101]. (See "Poliovirus vaccination", section on 'Adults'.)

Typhoid — Typhoid fever, a systemic febrile illness acquired from contaminated food or water, is prevalent in regions of Asia, Africa, and Latin America. A study that compared the outcomes of 80 pregnant women with typhoid with outcomes of 194 randomly selected women without typhoid reported that infection was not associated with an increased risk of adverse pregnancy outcome [102]. However, severe sequelae can occur; case reports have described in utero infection leading to pregnancy loss and preterm labor [103-105].

Typhoid vaccination is partially protective and is recommended for patients traveling to typhoid affected areas. Pregnant patients should avoid traveling to such areas, but can be immunized with the inactive, capsular polysaccharide vaccine (Typhim Vi) if such exposure is unavoidable. A live attenuated typhoid vaccine (Ty21a) is also available for oral use. It should be avoided in pregnancy because of the theoretical risk of adverse effects from in utero infection and because an alternative inactivated vaccine is available. There are minimal data on the use of typhoid vaccines during pregnancy [106].

Typhoid vaccination in the general population is discussed in detail elsewhere. (See "Immunizations for travel", section on 'Typhoid vaccine'.)

Other travel vaccines — The inactivated Japanese encephalitis vaccine, licensed for use in the United States in 2009, can be given to pregnant patients who are at substantial risk of disease exposure and where there are probable benefits of vaccination [107]. Although data on the risk of Japanese encephalitis virus (JEV) infection in pregnancy are limited, there are case reports of in utero infections and miscarriages in patients infected with JEV during early pregnancy [108,109]. There are no adequate studies of this vaccine safety during pregnancy. (See "Japanese encephalitis", section on 'Vaccination'.)

Rabies — The rabies vaccine, an inactivated vaccine, can be given as pre-exposure prophylaxis during pregnancy if the risk of exposure is substantial. Rabies vaccine can also be given, with or without rabies immune globulin, as postexposure prophylaxis following a rabies exposure during pregnancy [107,110]. (See "Rabies immune globulin and vaccine".)

Post-exposure prophylaxis — Certain vaccines are used for postexposure prophylaxis.

Vaccines without concern — If indicated, the hepatitis A and B, tetanus, and rabies vaccines can all be given to pregnant patients as part of postexposure prophylaxis management. (See 'Hepatitis A' above and 'Hepatitis B' above and 'Tetanus, diphtheria, and pertussis vaccination' above and 'Rabies' above.)

Vaccines used only in extenuating circumstances — In extenuating circumstances, the smallpox and anthrax vaccines, which would otherwise be avoided in pregnancy, can be given to pregnant patients following a direct exposure to prevent infection. These are typically only given in consultation with the CDC.

Smallpox — The smallpox vaccine is a live-virus vaccine (vaccinia virus) that is not used in the general population but may be indicated for certain individuals who participate in public health or smallpox response teams. If there are no cases of smallpox in the community, this vaccine is contraindicated in pregnancy, and pre-exposure smallpox vaccination is not recommended for those who are pregnant (in any trimester), contemplating pregnancy within 28 days, breastfeeding, or close contacts (eg, household member, sex partner) of patients who are pregnant or contemplating pregnancy within 28 days [107,111-113]. A pregnancy test is recommended for females of childbearing potential before receiving a smallpox vaccine, and patients who are pregnant should not have close or physical contact with anyone who has received the smallpox vaccine in the preceding 28 days. There has been one case report of transmission of vaccinia from a recently vaccinated husband to his nursing wife, followed by mother to child transmission [114].

However, in the event of a documented exposure to smallpox, a smallpox outbreak, or intentional release of the smallpox virus, the recommendations are different, and pregnant patients who have had a definite direct exposure (eg, face-to-face, household, or close-proximity contact with a smallpox patient) should be vaccinated because of the lethality of the disease [113]. Under these circumstances, vaccination should be performed only with consultation from the CDC. The vaccinia virus can be transmitted in breast milk. Thus, if vaccination is indicated in a nursing mother, they should stop breastfeeding until the vaccination scab sloughs off [115].

The major pregnancy-related concern with smallpox immunization is the possibility of fetal vaccinia, which is rare, but associated with a high rate of fetal loss. In a 2015 systematic review of risks from smallpox vaccination during pregnancy, only 21 cases of fetal vaccinia, reported from 1809 to 1985, were identified in the literature; only three cases survived [116]. There is no known reliable intrauterine diagnostic test to confirm fetal infection. If a patient becomes pregnant within four weeks of vaccination, they should be counseled about fetal risks [112]. The CDC does not recommend routine use of vaccinia immune globulin (VIG) prophylaxis to reduce the risk of fetal vaccinia in such cases, as the efficacy of this approach has not been proven [117,118]. On the other hand, VIG should not be withheld if a pregnant patient develops a condition where VIG is needed.

Otherwise, in the same systematic review mentioned above, smallpox vaccination was not associated with spontaneous abortion, preterm birth, or stillbirth [116]. Although first trimester vaccination was associated with a small increase in congenital anomalies compared with unvaccinated women (2.4 versus 1.5 percent, pooled RR 1.34, 95% CI 1.02–1.77), no specific pattern of defects was observed and there appeared to be publication bias for this outcome. Smallpox vaccination is not considered an indication for pregnancy termination. Nonpregnancy-related complications of smallpox vaccination are discussed separately. (See "Vaccines to prevent smallpox, mpox (monkeypox), and other orthopoxviruses" and "Variola virus (smallpox)".)

The CDC maintains an internet site with information on smallpox vaccination and pregnancy (https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5212a6.htm). Pregnant patients who are vaccinated should be asked to participate in a voluntary registry of such individuals (National Smallpox Vaccine in Pregnancy Registry, telephone 404-639-8253).

Anthrax — Bacillus anthracis is a spore-forming bacterium that could cause a zoonotic infection. Because B. anthracis spores remain viable for a long time and can be aerosolized, anthrax has also been identified and used as a biologic weapon agent. An inactivated subunit anthrax vaccine (AVA) is available in the United States. It is not used in the general population, but pre-exposure prophylaxis with the vaccine is recommended by the CDC for individuals at high risk, such as those with occupations that may expose them to anthrax (eg, laboratory workers, outbreak investigators, and military personnel who are at increased risk of anthrax exposure) [119]. However, such pre-exposure anthrax vaccination is not recommended for pregnant patients and should be deferred, if indicated, until after pregnancy [119]. Pregnancy is a United States Department of Defense exemption for pre-exposure anthrax vaccination.

However, in the event of a high-risk exposure to aerosolized B. anthracis spores, pregnant patients should receive postexposure prophylaxis (PEP) with AVA and 60 days of antimicrobial therapy. In the postexposure setting, AVA is administered as a three-dose subcutaneous series, with the first dose administered as soon as possible and the second and third doses administered two and four weeks after the first dose. Antimicrobial regimens for postexposure prophylaxis of anthrax are discussed elsewhere. (See "Prevention of anthrax", section on 'Antimicrobial regimen selection'.)

Data on the use of AVA during pregnancy are generally reassuring, although a slightly increased risk of congenital anomalies cannot be ruled out. In a study of over 1,154,000 infants born to women in the military, including 37,140 born to women who had ever received AVA, congenital anomalies were slightly more common in first trimester-exposed infants compared with infants of women vaccinated outside of the first trimester (OR 1.18, 95% CI 0.997-1.41), never-vaccinated (OR 1.20, 95% CI 1.02-1.42), or vaccinated postpartum (OR 1.02, 95% CI 1.01-1.43) [120]. Although a causal association is unlikely, the possibility cannot be completely excluded. Another study of 4092 women in the military (3136 of whom had received at least one dose of vaccine) found no difference in pregnancy rate or odds of having a live birth with vaccine receipt [121]. The study, however, was not powered sufficiently to detect a small but significant effect on birth outcomes.

There are no data on the use of AVA among breastfeeding patients. Administration of other inactivated vaccines during breastfeeding is not medically contraindicated so breastfeeding is not considered a contraindication to vaccination, when indicated [119].

COVID-19 vaccination — Numerous vaccines have been shown to be safe and effective at preventing coronavirus disease 2019 (COVID-19) in pregnant and breastfeeding patients [122-126]. We recommend not withholding messenger ribonucleic acid (mRNA) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines on the basis of pregnancy/lactation alone for those who are at risk for COVID-19 acquisition or complications, or who are eligible for and desire vaccination. This is discussed in detail separately. (See "COVID-19: Vaccines" and "COVID-19: Overview of pregnancy issues", section on 'Vaccination in people planning pregnancy and pregnant or recently pregnant people'.)

IMMUNIZATIONS TO AVOID DURING PREGNANCY

Human papillomavirus — Several inactivated human papillomavirus (HPV) vaccines are available worldwide (bivalent, quadrivalent, and 9-valent); in the United States, only the 9-valent HPV vaccine (Gardasil-9) is recommended for the nonpregnant population. Administration of any HPV vaccine during pregnancy is not recommended because of limited information about safety [127]. If a patient is found to be pregnant after initiating the vaccination series, the remaining doses should be delayed until after pregnancy [128]. However, they can be reassured that available evidence on inadvertent vaccination during pregnancy does not indicate any increased risk of adverse pregnancy outcome. A detailed discussion of HPV vaccines, including vaccine schedule, can be found separately. (See "Human papillomavirus vaccination".)

Most data on the use of HPV vaccine during pregnancy are for the quadrivalent HPV (qHPV) vaccine [129-134]. Among 3819 patients who became pregnant while enrolled in the qHPV vaccine trials, the composite rate of adverse pregnancy outcome (spontaneous abortion, late fetal death, congenital anomaly) was similar in those who received the vaccine versus the placebo (22.6 versus 23.1 percent) [129]. In a population-based study of all pregnancies in Denmark over an eight-year period, which included nearly 7500 women with exposure to at least one dose of qHPV vaccine during pregnancy and with over 5000 births, exposure to qHPV was not associated with an increased rate of spontaneous abortion, stillbirth, or infant mortality; no association was identified between spontaneous abortion and the number or timing of doses [135]. Similarly, in a cohort study using the national patient registry in Denmark, the risks of major congenital anomalies (odds ratio [OR] 1.19, 95% CI 0.9-1.58), preterm birth (OR 1.15, 95% CI 0.9-1.42), and low birth weight (OR 1.10, 95% CI 0.85-1.43) were comparable among approximately 1700 women who received quadrivalent HPV vaccine during pregnancy (mostly during the first trimester) and 7000 matched controls who did not [133].

A few offspring with congenital anomalies (one pyloric stenosis with ankyloglossia, one congenital hydronephrosis, one congenital megacolon, one club foot, and one hip dysplasia) have been reported among women who received quadrivalent HPV vaccine within 30 days of the estimated time of conception, but an expert panel deemed these to be unrelated to vaccine exposure [130,131].

Data for the 9-valent HPV vaccine are more limited, but emerging and similarly reassuring [136-139]. In a combined analysis of seven phase-III clinical trials of the 9-valent HPV vaccine, inadvertent vaccine doses during pregnancy were given to 1435 patients with a known pregnancy outcome [136]. For pregnancies with onset within 30 days before or after vaccination, spontaneous abortion rates were higher for the 9-valent HPV than the qHPV vaccine but within the range reported for pregnant women (≤33 percent for pregnancies detected with beta-human chorionic gonadotropin [beta-hCG]). None of the congenital anomalies observed were considered vaccine-related, and no congenital anomaly was reported in pregnancies with expected date of confinement within 30 days before or after a vaccination with 9-valent HPV vaccine. In another observational study including 1493 pregnant patients, those receiving the 9-valent HPV vaccine near the time of conception or during pregnancy compared with >16 weeks prior to conception had similar rates of spontaneous abortions, stillbirths, preterm births, or small for gestational age births [139].  

A pregnancy registry has been established for the 9-valent HPV vaccine (1-800-986-8999) [140].

Similar findings have been reported for the bivalent HPV vaccine [141,142].

Measles, mumps, rubella — The measles, mumps, rubella (MMR) vaccine, a live attenuated vaccine, should not be given to pregnant patients. Because of the maternal morbidity and adverse pregnancy outcomes associated with measles and rubella infections during pregnancy, establishing immunity prior to conception is an important part of management of females of childbearing age. (See 'Preconception immunization' above.)

Because pregnant patients might be at a higher risk for severe measles and measles complications, postexposure prophylaxis is recommended for pregnant patients who are measles nonimmune and had an exposure to measles [18]. In such cases, intravenous immune globulin at a dose of 400 mg/kg is recommended within six days of exposure. (See "Measles, mumps, and rubella immunization in adults", section on 'Post-exposure prophylaxis'.)

Pregnant patients without evidence of immunity to rubella (or measles) should receive the MMR vaccine postpartum, ideally prior to discharge but after delivery. The vaccine can be given safely to postpartum patients who are breastfeeding. Although rubella virus is excreted into breast milk, only seroconversion without serious infection has been reported in breastfeeding infants [143]. (See 'Postpartum immunization' below.)

MMR may be given to household members of pregnant patients (eg, children), when indicated, without risk to the mother or fetus, since infection is not transmitted from immunized individuals [17].

The MMR vaccine is not given during pregnancy because of a theoretical risk of live vaccines to the mother or fetus, although data have not demonstrated a certain risk. No congenital rubella syndrome-like defects (eg, hearing loss, cataracts, cardiac abnormalities, bone lesions, growth restriction, and neurologic abnormalities, including intellectual disability) have been observed in the offspring of patients inadvertently vaccinated just before or during pregnancy [13,17,144,145]. Similarly, there were no adverse outcomes clearly attributable to measles following vaccination. Termination of pregnancy after inadvertent vaccination should not be recommended solely on the basis of a theoretical risk of embryopathy [17,146].

Varicella — The varicella vaccine used for primary varicella prevention is a live attenuated vaccine. As with other live vaccines, varicella vaccine should not be administered to pregnant patients. A congenital varicella syndrome occurs in 1 to 2 percent of cases of maternal varicella (primary chickenpox) infection. Because of the maternal morbidity and adverse pregnancy outcomes associated with varicella infection during pregnancy, establishing immunity prior to conception is an important part of management of females of childbearing age [147]. (See 'Preconception immunization' above.)

For postexposure prophylaxis in nonimmune pregnant patients who have had an exposure to varicella, varicella-zoster immune globulin is indicated with postpartum vaccination at least five months after receipt of immune globulin. (See "Varicella-zoster virus infection in pregnancy", section on 'Post-exposure prophylaxis'.)

Pregnant patients without evidence of immunity to varicella should receive the varicella vaccine postpartum, ideally prior to discharge after delivery. There are minimal data regarding the safety of breastfeeding after varicella vaccination. A study of 12 nursing mothers given varicella vaccine postpartum did not detect varicella deoxyribonucleic acid (DNA) in samples of postvaccination breast milk and none of their infants seroconverted or had evidence of varicella virus DNA [148]. Varicella vaccine is reasonable for a nursing mother, extrapolating from this study and the observation that no harm has been demonstrated from other live attenuated vaccines given to lactating patients [15]. (See 'Postpartum immunization' below.)

Routine varicella immunization of the children of susceptible pregnant patients is not contraindicated. The risk of transmission of vaccine virus from a healthy individual to a susceptible household contact is low. (See "Varicella-zoster virus infection in pregnancy", section on 'Household contacts of pregnant women'.)

The varicella vaccine is not given during pregnancy because of a theoretical risk of live vaccines to the mother or fetus, although data have not demonstrated a certain risk. Data from a VARIVAX registry showed that from inception of the registry in 1995 through March 2012, no cases of congenital varicella syndrome and no increased prevalence of other congenital anomalies were detected in over 900 women vaccinated within three months before or during pregnancy [147,149]. The cohort included 95 live-born infants of varicella-susceptible women exposed during the first and second trimesters, which are the high-risk period for congenital varicella syndrome (95% CI for congenital infection risk in this cohort 0-3.8 percent). Although a small risk for congenital varicella syndrome cannot be ruled out, these findings support the conclusion that pregnancy termination solely because of varicella vaccination during the gestation is unwarranted [15,20].

MMRV vaccine — A combination measles, mumps, rubella, and varicella vaccine (MMRV, Oka/Merck, ProQuad) became available in 2005. It is indicated for simultaneous immunization against measles, mumps, rubella, and varicella among children 12 months to 12 years of age and is used in place of trivalent MMR vaccine and monovalent varicella vaccine. Although not intended for adults, the issues described above for MMR and varicella immunization apply to this vaccine if administered to an adult since it is composed of live, attenuated virus. (See 'Measles, mumps, rubella' above and 'Varicella' above.)

LAIV — Pregnancy has always been a contraindication to use of the live attenuated influenza vaccine (LAIV), even though no unusual patterns of pregnancy complications or adverse fetal outcomes were observed in the database of the Vaccine Adverse Event Reporting System [150,151]. Pregnant patients do not need to avoid contact with persons immunized with LAIV [152].

Tuberculosis — Use of BCG vaccine (Bacillus Calmette Guerin) to prevent tuberculosis is not recommended during pregnancy, although no harmful effects have been shown [153]. (See "Vaccines for prevention of tuberculosis".)

Zoster — While the Advisory Committee on Immunization Practices (ACIP) recommends administering the recombinant zoster vaccine (RZV) to all immunocompromised adults between the ages of 19 to 49 and to all adults ≥50 years of age, the ACIP does not provide a recommendation on RZV administration during pregnancy [154]. Thus, for immunocompromised pregnant individuals, we suggest deferring RZV until after pregnancy, when possible, given a lack of safety data. No data are available on pregnancy outcomes in patients exposed to RZV [155]. Studies of RZV in pregnant rats did not show adverse effects [156].

Zoster vaccine live (ZVL) is a live vaccine that should not be administered to pregnant patients or those trying to conceive; ZVL is no longer available in the United States.

POSTPARTUM IMMUNIZATION — Indications and procedures for vaccination of postpartum patients are those described for the general population. Both inactivated and live vaccines (except smallpox and yellow fever vaccine) may be administered to nursing caregiver, and breastfeeding does not adversely affect success or safety of vaccination [15,157]. Smallpox and yellow fever vaccines are avoided in nonemergency situations because breastfed infants of vaccinated nursing caregivers are at risk of developing vaccinia and meningoencephalitis, respectively [89,98].

●MMR and varicella – The following vaccines should be given before discharge to protect a nonimmune mother and newborn:

•MMR – The measles, mumps, rubella (MMR) vaccine should be administered to patients nonimmune to rubella or measles [8] (see 'Preconception immunization' above). If a patient has documented receipt of one or two doses of rubella-containing vaccine but has rubella serology that is not clearly positive, they should receive one additional dose of MMR vaccine (maximum of three doses) and do not need to be retested for serologic evidence of rubella immunity [17]. If measles vaccination history could not be documented, and the measles immunoglobulin G (IgG) is negative, nonpregnant patients should receive one or two doses of the MMR vaccine based on their risk category. (See "Measles, mumps, and rubella immunization in adults".)

•Varicella – Varicella vaccination is recommended for patients without evidence of immunity [158]. The first dose is given while the patient is in the hospital and the second dose is given four to eight weeks later, which typically coincides with the routine postpartum visit. Breastfeeding is not a contraindication to administration.

For RhD-negative individuals who received anti-D immune globulin postpartum, MMR and/or varicella vaccine is still administered immediately postpartum, when indicated [15]. A theoretical concern is the possibility that anti-rubella antibodies may be present in sufficient concentration in anti-D immune globulin to inhibit the patient’s immune response to the rubella vaccine. However, there is evidence that anti-D immune globulin does not reduce the response to the rubella vaccine [159-163], and there are no published reports of rubella vaccine failure after administration of anti-D immune globulin. Nevertheless, the United States Centers for Disease Control and Prevention suggests that patients who have received both anti-D immune globulin and rubella vaccine be serologically tested after vaccination, if feasible, to ensure that seroconversion has occurred [15,164]. The Advisory Committee on Immunization Practices recommends waiting ≥3 months before evaluating the immune response [15]. (See "Assessing antibody function as part of an immunologic evaluation", section on 'Interfering factors'.)

●HPV – Eligible patients who have not been previously vaccinated against human papillomavirus (HPV), or who have not completed the vaccine series, may receive the vaccination postpartum [165]; the vaccine can be safely given to those patients who are breastfeeding. (See "Human papillomavirus vaccination".)

●Tdap – If not given as recommended during pregnancy, Tdap should be given postpartum to patients who have not previously received Tdap [24]. This reduces the risk of maternal pertussis, and thus transmission to the infant, in whom pertussis can be lethal or have significant morbidity. However, the maternal immune response may not be sufficiently rapid to provide indirect protection to the infant until two weeks post-immunization [26]. Breastfeeding is not a contraindication to administration. (See 'Tetanus, diphtheria, and pertussis vaccination' above.)

●Live attenuated influenza vaccine (LAIV) – LAIV is contraindicated in pregnancy but was offered to postpartum patients (including breastfeeding patients) in the past. It was not recommended during the 2016-2017 and 2017-2018 influenza seasons to any individual in the United States because of its low efficacy [166], but it was reintroduced in the 2018-2019 season. (See "Seasonal influenza vaccination in adults", section on 'Choice of vaccine formulation'.)

Although postpartum patients can receive LAIV where it is an option recommended by local health authorities, there is a possibility that a caregiver recently vaccinated with LAIV can infect their neonate by shedding the vaccine virus, given the close contact between caregivers and newborns [167]. Breastfeeding is not a contraindication to LAIV, although specific information regarding excretion in breast milk is not available [168].

IMMUNE GLOBULINS — Immune globulins are given to prevent or reduce the severity of certain diseases in special circumstances. There are no known risks for the fetus from passive immunization of pregnant patients with immune globulin preparations [15]. Postexposure prophylaxis of hepatitis A and B, rabies, and tetanus is not altered by pregnancy.

Pregnancy is an indication for measles postexposure prophylaxis with immune globulin since pregnant patients might be at higher risk for developing severe measles and complications. Pregnant patients should receive immune globulin intravenously, rather than intramuscularly, in order to administer doses high enough to achieve protective levels of measles antibody titers [17]. (See "Measles, mumps, and rubella immunization in adults", section on 'Post-exposure prophylaxis'.)

Pregnancy is also an indication for postexposure prophylaxis of varicella with varicella immune globulins. This is reviewed separately. (See "Varicella-zoster virus infection in pregnancy", section on 'Post-exposure prophylaxis'.)

VACCINES UNDER INVESTIGATION — The following vaccines are undergoing investigation for use during pregnancy and are not yet available for clinical use:

●Respiratory syncytial virus – Respiratory syncytial virus (RSV) is a major cause of morbidity and mortality in infants (see "Respiratory syncytial virus infection: Clinical features and diagnosis", section on 'Epidemiology'). RSV vaccination of pregnant patients to provide passive immunity to the infant is undergoing evaluation but is not currently recommended in pregnancy.

In an interim analysis of a phase 2b randomized trial evaluating the safety and efficacy of RSV immunization in pregnancy, 406 pregnant patients between 24 and 36 weeks gestation received either a single intramuscular injection of RSV prefusion F protein-based vaccine (120 μg or 240 μg and with or without aluminum hydroxide) or placebo and were followed through the 2019 to 2020 RSV season [169]. Infants of vaccinated mothers (any dose) had a lower rate of RSV-associated medical illness compared with infants of unvaccinated mothers (0.7 versus 4.9 percent, observed vaccine efficacy 84.7 percent); rates of severe RSV-associated illness also trended lower in infants of vaccinated mothers but were not statistically significant. Serious adverse events in pregnant patients and infants were similar between groups. The study is ongoing.

●Group B streptococcus – Vaccines against group B streptococcus are also undergoing evaluation. This is discussed elsewhere. (See "Vaccines for the prevention of group B streptococcal disease".)

●Cytomegalovirus – Cytomegalovirus (CMV) is a common congenital viral infection and can lead to significant infant morbidity (eg, deafness) (see "Cytomegalovirus infection in pregnancy"). Development of maternal CMV vaccination to reduce the incidence of congenital CMV infection has been ongoing and phase 2 and 3 studies are underway [170,171].

SELECTED RESOURCES FOR UNITED STATES CLINICIANS

●United States Centers for Disease Control and Prevention (CDC) vaccines webpage

●CDC guidelines on vaccines and pregnancy

●CDC adult immunization schedule

●CDC information on Vaccine administration

●CDC information on Vaccine storage and handling

●American College of Obstetricians and Gynecologists (www.immunizationfor women.org)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Pertussis" and "Society guideline links: Immunizations in adults" and "Society guideline links: Diphtheria, tetanus, and pertussis vaccination".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Avoiding infections in pregnancy (The Basics)" and "Patient education: Vaccines and pregnancy (The Basics)" and "Patient education: Tdap vaccine (The Basics)")

●Beyond the Basics topics (see "Patient education: Vaccination during pregnancy (Beyond the Basics)" and "Patient education: Avoiding infections in pregnancy (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Preconception immunization

•Ideally, patients should be vaccinated against preventable diseases in their environment prior to conception according to the recommended adult immunization schedule (figure 1 and figure 2). (See 'Overview of immunization' above.)

•For susceptible patients of childbearing age who may become pregnant, ensuring immunity against measles, mumps, rubella, and varicella is important since these immunizations are contraindicated during pregnancy and for a defined period before conception, and infection in nonimmune pregnant patients can adversely affect pregnancy outcome. (See 'Preconception immunization' above.)

•Before administering any vaccine, reasonable practices include asking a patient if they are pregnant or could become pregnant in the next four weeks and counseling them about the potential risks of vaccination during pregnancy or just before conception.

•Routine pregnancy testing of patients of childbearing age before administering a vaccine, even a live-virus vaccine, is not necessary if pregnancy can reasonably be excluded by history. (See 'Preconception immunization' above.)

•Live vaccines are generally avoided during pregnancy because of a theoretical risk to the fetus. Pregnancy should be avoided for 28 days following administration of a live vaccine. However, when pregnancy occurs within one month of immunization with the live measles, mumps, rubella (MMR) vaccine, varicella vaccine, yellow fever vaccine, or oral polio vaccine, teratogenesis has not been reported. Therefore, termination of pregnancy for exposure to these vaccines is unwarranted. (See 'Live vaccines' above and 'Preconception immunization' above.)

●Minimizing exposure − Pregnant patients should minimize their risk of exposure to infections to which they are susceptible by avoiding travel to high-risk locations (eg, areas where yellow fever is prevalent), assuring that household members are immunized according to standard immunization schedules, and maintaining good hygienic practices. (See 'Minimizing risks of infection exposure' above.)

●Routine prenatal immunizations

•All patients who are pregnant during influenza season should receive the inactivated influenza vaccine. Influenza is particularly morbid in pregnant patients. Maternal immunization also provides passive protection to infants in the first few months of life when they cannot be vaccinated themselves. (See 'Inactivated influenza vaccine' above and "Seasonal influenza and pregnancy".)

•We recommend administration of the tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) to all pregnant patients in each pregnancy between 27 and 36 weeks of gestation (and preferably during the earlier part of this period), even if the patient has a previous history of pertussis or vaccination (Grade 1B). Tdap is given to reduce the risk of maternal pertussis, and thus transmission to the infant, in whom pertussis can be lethal or have significant morbidity. Placental transfer of maternal antibodies may provide passive protection of the infant against pertussis. (See 'Tetanus, diphtheria, and pertussis vaccination' above.)

●Other vaccines for selected patients − Pregnant patients with comorbidities or exposures that place them at high risk for hepatitis A, hepatitis B, pneumococcal, Haemophilus influenzae b, or meningococcal infections should receive these immunizations. Certain formulations of some of these vaccines are not recommended for use during pregnancy because of limited safety data. (See 'Pre-exposure prophylaxis' above.)

●Travel vaccines − If travel to high-risk areas cannot be avoided, inactivated travel vaccines, such as for hepatitis A, poliovirus, and typhoid fever, should be administered prior to travel. If the risk of yellow fever exposure is expected to be higher than the risk of vaccination, the yellow fever vaccine, a live attenuated vaccine, can be administered during pregnancy in consultation with an infectious disease specialist. In cases where the risk of disease is low but vaccination is an international travel requirement, a medical waiver can be issued. Patients who received the yellow fever vaccine during pregnancy are not considered immune for life and require another vaccine if traveling to a high-risk area again. (See 'Poliovirus' above and 'Typhoid' above and 'Yellow fever' above and 'Other travel vaccines' above.)

●Immunizations to avoid during pregnancy – Pregnant patients should avoid live vaccines (eg, measles, mumps, rubella, varicella, live influenza vaccine) due to the theoretical risk to the fetus. Other vaccines, such as human papillomavirus (HPV) or the recombinant zoster vaccine are not recommended during pregnancy due to limited data on vaccine safety. (See 'Immunizations to avoid during pregnancy' above.)

●Postpartum immunization

•Both inactivated and live vaccines (except smallpox and yellow fever vaccine) may be administered to postpartum patients and nursing caregivers; breastfeeding does not adversely affect success or safety of vaccination. Smallpox and yellow fever vaccines are avoided in nonemergency situations because breastfed infants of vaccinated nursing caregivers are at risk of developing vaccinia and meningoencephalitis, respectively. (See 'Postpartum immunization' above.)

•All non-immune postpartum patients should receive the MMR, varicella, TdAP, and influenza vaccines prior to leaving the hospital to provide protective immunity for both the mother and the child. HPV can be administered as well if the patient has not started or completed the vaccination series. (See 'Postpartum immunization' above and 'Tetanus, diphtheria, and pertussis vaccination' above and 'Inactivated influenza vaccine' above and 'MMRV vaccine' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Vanessa A Barss, MD, FACOG, who contributed to an earlier version of this topic review.