Vaccination in Pregnancy

Zain A Al-Safi; Valerie I Shavell; Bernard Gonik


Women's Health. 2011;7(1):109-119. 

In This Article

Vaccination Guidelines

In the USA, the The Advisory Committee on Immunization Practices (ACIP) establishes recommendations for vaccine administration in consultation with experts and governmental agencies. These vaccination guidelines are periodically updated and are endorsed by professional organizations, including the American College of Obstetricians and Gynecologists (ACOG).[17] ACIP recommendations for vaccination against specific infections that may affect pregnant women and their newborn infants are discussed.

Hepatitis A

Hepatitis A is a RNA virus that is transmitted via the fecal–oral route. Infection with hepatitis A may manifest as symptoms such as fever, malaise, anorexia, nausea, abdominal discomfort and jaundice.[18] Symptoms typically resolve within 2 months; however, a small percentage of individuals may be affected by a prolonged or relapsing course. Infection with hepatitis A during pregnancy may be associated with serious complications such as preterm labor.[19] Vertical transmission of hepatitis A infection also has been described.[20]

Although data on the safety of the hepatitis A vaccination during pregnancy are limited, pregnancy is not a contraindication to vaccination against hepatitis A. The vaccine is produced from an inactivated virus; therefore, the theoretical risk associated with vaccination during pregnancy is expected to be low.[18] If a woman is anticipated to be at high risk for contracting hepatitis A (e.g., travel to an area where hepatitis A is endemic, such as Central and South America, Africa, Middle East, Asia and Western Pacific), the vaccine is typically recommended.

The hepatitis A vaccine is available as both a single-antigen vaccine and as a combination vaccine containing both hepatitis A virus (HAV) and hepatitis B virus antigens. Both vaccines use inactivated HAV and the hepatitis B virus component is a recombinant protein nonviral antigen. There are currently two available HAV vaccines that are given in two doses, either 6–12 months apart or 6–18 months apart. The combination vaccine is given in three doses at 0, 1 and 6 months.[21] Immune globulin remains available for postexposure prophylaxis, although primary vaccine-based prevention is preferred.[21,22]

Hepatitis B

Hepatitis B is a bloodborne DNA virus. Symptoms, when present, may include anorexia, malaise, nausea, vomiting, abdominal pain and jaundice. Those chronically infected are most severely affected and are the primary reservoir for hepatitis B transmission. Unfortunately, 90% of infants infected with hepatitis B become chronically infected.[23] Perinatal transmission from infected mothers and infection from household contacts are the primary sources of infection in early infancy.

Vaccination to prevent hepatitis B infection is extremely important. Ideally, women should be vaccinated prior to pregnancy. However, if a woman did not receive prior vaccination, the hepatitis B vaccine is composed of a noninfectious viral particle and should cause no harm to the developing fetus.[24,25] Therefore, the ACIP recommends counseling pregnant women who may be at high risk for acquiring hepatitis B about vaccination during pregnancy.[23] Those at high risk include women with multiple sex partners or a recent sexually transmitted disease, current injection drug users, or women who have a partner infected with hepatitis B. Nearly 80% of new infections are associated with high-risk sexual behavior or injection drug use.[17]


Influenza is caused by a group of RNA viruses that belong to the family Orthomyxoviridae.[26] The influenza viruses are classified into three genera: influenza A, B and C. Sore throat, fever and cough are the most frequent symptoms. The rate of serious illness and hospitalization is increased four- to five-fold during pregnancy.[27] Newborns and young infants are also at high risk for hospitalization as well as complications such as secondary bacterial pneumonia and otitis media.[28,29]

The inactivated influenza vaccine has been administered during pregnancy in the USA since the 1960s.[28] As the influenza vaccine has minimal immunogenicity prior to 6 months of age, maternal vaccination during pregnancy has the potential to decrease neonatal influenza. In fact, in one study, immunization during pregnancy was shown to reduce the incidence of laboratory-confirmed influenza in infants up to 6 months of age by 63% as well as lessen febrile influenza-like illness by approximately a third in both young infants and mothers.[29] Only five women, therefore, would need to be vaccinated during pregnancy to prevent a single case of febrile influenza-like illness in a mother or an infant.

Advisory Committee on Immunization Practices and ACOG recommend administration of the trivalent-inactivated influenza vaccine to women who will be pregnant during the influenza season (October through to May) regardless of gestational age.[30,31] Immunization is especially important for women who will be in their third trimester or who will have infants under the age of 6 months during the influenza season.[28] Immunization with the live-attenuated influenza vaccine is not advised during pregnancy.[25] Although these recommendations have been put forth, a suboptimal number of pregnant women ultimately receive the influenza vaccine (Figure 2).[32] Interventions to increase awareness of the importance of the influenza vaccine during pregnancy are necessary.

Figure 2.

Percentage of women with live births who reported receiving the influenza vaccine during pregnancy in Georgia and Rhode Island (USA).
Adapted from [59].

The H1N1 virus is a specific subtype of influenza A that was determined to be responsible for a worldwide influenza pandemic that began in 2009. The viral strain responsible for the pandemic originated from a reassortment of several swine strains, a human strain and an avian strain.[26] The genetic shift involved in the emergence of the novel H1N1 strain limits the ability of the immune system to recognize and destroy the virus. As with seasonal influenza, cough, fever, headache, sore throat, rhinorrhea, chills and muscle aches are the most common symptoms.[33] Pregnant women are at high risk for influenza-related complications.[34] Furthermore, the mortality rate appears to be higher in pregnant women, particularly if infection occurs in the third trimester.[35]

Vaccines for H1N1 became available in 2009 in both live-attenuated and inactivated formulations, and pregnant women were one of the initial target groups for immunization with the inactivated vaccine.[33,36] The USA 2010–2011 influenza vaccine will protect against an H3N2 virus, an influenza B virus and the 2009 H1N1 influenza.[103]


Streptococcus pneumonia (pneumococcus) has the potential to colonize the upper respiratory tract, resulting in upper respiratory tract infections, pneumonia or disseminated infections such as bacteremia and meningitis.[37] Morbidity from pneumonia is increased during pregnancy, likely due to physiological respiratory and cardiovascular changes associated with parturition.[25] Premature labor is also associated with maternal pneumonia during pregnancy.

In addition to preventing pneumococcal infection in pregnancy, immunization during pregnancy is a strategy that can provide young infants protection from these pathogens. Administration of pneumococcal polysaccharide vaccine to women in the third trimester of pregnancy was safe and well tolerated.[38] Efficient transplacental passage of vaccine-induced pneumococcal antibodies was documented with concentrations of pneumococcal antibodies in infants at birth similar to those in their mothers.[38]

Increased concentrations of IgA antibodies have been found in breast milk after maternal immunization with the pneumococcal vaccine,[39] demonstrating that immunity may be conferred to the newborn infant through this route as well. Women who are at high risk for contracting pneumococcus (e.g., those who are immunosuppressed, have had a splenectomy, or who have sickle-cell disease) and who have not previously received the pneumococcal vaccine are candidates for vaccination during pregnancy.[25]


Poliomyelitis is caused by one of three serotypes of the poliovirus. The majority of poliovirus infections are asymptomatic. In those who are symptomatic, fever may be followed by aseptic meningitis or paralytic disease.[40] If a woman is infected during pregnancy, neonatal mortality approaches 40%.[25] Fortunately, poliomyelitis has been nearly eradicated in the western world with the development of vaccines against polio in the 1950s. However, polio remains endemic in several countries (Nigeria, India, Pakistan and Afghanistan).[41]

There are two polio vaccines available: the inactivated vaccine and the live-attenuated oral vaccine. The live-attenuated oral vaccine is reserved for the control of polio outbreaks and endemic communities. The live-attenuated polio vaccine has been studied in pregnancy and has proven to be a safe alternative to the inactivated vaccine to be given to unimmunized or partially immunized pregnant individuals.[42] Although no adverse outcomes have been associated with the inactivated or live-attenuated oral polio vaccines when given during pregnancy, vaccination should be avoided on theoretical grounds unless necessary.[25,40] Therefore, if a pregnant woman requires immediate protection, the inactivated or live-attenuated polio vaccine may be considered, with preference given to the nonlive vaccine. If the woman is aged 18 years or older, the inactivated polio vaccine should be given in a three-dose series – the second dose 4–8 weeks after the first and the third dose 6–12 months after the second.[40]

Measles, Mumps & Rubella

Infection with the measles virus typically leads to fever, cough, rhinorrhea and a generalized rash. Complications include diarrhea, bronchopneumonia and encephalitis, which may result in permanent brain damage. Measles infection during pregnancy is associated with miscarriage, premature labor and low infant birth weight.[43]

Painful swelling of the salivary glands, classically the parotid glands, is the presenting symptom in the majority of infections with the mumps virus. Swelling of the salivary glands may precede fever, headache, malaise, myalgia and anorexia. Although serious complications, such as meningoencephalitis, may occur, mumps is typically a mild and self-limited illness. Mumps infection in the first trimester of pregnancy is associated with an increased risk of fetal death.[43]

Infection with the rubella virus typically manifests as fever and malaise followed by a rash that begins on the face and spreads to the trunk and extremities. Complications such as arthralgia, encephalitis and thrombocytopenic pupura may result, particularly in adults.[44] Congenital rubella is a severe condition that is associated with deafness, cataracts, cardiac defects, microcephaly, mental retardation and hepatosplenomegaly. Congenital rubella may affect up to 85% of fetuses infected in the first trimester.[44]

Before vaccination against rubella became available in the USA, approximately 20,000 cases of congenital rubella syndrome occurred during a rubella epidemic from 1964 to 1965.[43] Due to the potential for congenital rubella syndrome, vaccination against rubella prior to pregnancy is particularly important. As the rubella vaccine given alone or in combination with measles and mumps is a live vaccine, pregnancy should be delayed for 1–3 months after immunization. Furthermore, immunization is contraindicated during pregnancy. Inadvertent vaccination during pregnancy, however, is not an indication for termination as no deleterious effects on the developing fetus have been confirmed.[44] Women who are discovered not to be immune to rubella during pregnancy should be vaccinated in the immediate postpartum period. Breastfeeding is not a contraindication to vaccination.

Tetanus, Diptheria & Pertussis

Tetanus occurs when Clostridium tetani spores enter the body through disrupted skin or mucus membranes. Lockjaw, rigidity and painful skeletal muscle contraction ensue, which may eventually result in respiratory failure, autonomic instability and death.[45] Tetanus during pregnancy or within 6 weeks of termination of pregnancy is defined as obstetric tetanus. Fatality rates for obstetric tetanus vary widely in the literature, with the highest fatality rates in locations where access to medical care is limited.[45] Neonatal tetanus may also occur, primarily from contamination of the umbilical cord stump. Infants who survive may be affected with permanent neurologic impairment.

Diphtheria is a severe respiratory infection caused by Corynebacterium diphtheriae. Diphtheria is classically associated with gray-tinged respiratory mucosa. Airway obstruction may occur as well as cardiac, neurologic or renal dysfunction mediated by the production of diphtheria toxin.

Pertussis is a prolonged respiratory infection caused by the Gram-negative coccobacillus Bordetella pertussis. Pertussis is transmitted via respiratory droplets. More than 50% of cases of pertussis in early infancy may be traced to parents infected with B. pertussis.[46] Infants have the highest complication and fatality rates.

In 2005, two tetanus-reduced diphtheria and acellular pertussis (Tdap) vaccines were licensed for use in the USA. These vaccines provide added coverage for pertussis and are designed for single-dose use in place of the next dose of the tetanus and diphtheria toxoids vaccine (Td). Administration of Tdap during routine wellness visits, when indicated, is the preferred strategy to ensure protection from tetanus, diphtheria and pertussis. Pregnancy need not be delayed after vaccination with Tdap as the vaccine only contains toxoids and purified bacterial components.[45] Pregnancy is not a contraindication to Tdap vaccine and in special situations, Tdap may be administered during pregnancy (i.e., exposure to a pertussis outbreak). However, women must be counseled that there is a lack of data on the safety of Tdap in pregnancy and administration is generally delayed until after the first trimester despite there being no data demonstrating an adverse effect in early pregnancy. Women who have not previously received the Tdap vaccine should be counseled for immunization in the immediate postpartum period, and it may be administered as soon as 2 years after the most recent Td vaccination.[45] Any adults or adolescents who will be in contact with an infant should receive Tdap as well.

If more than 10 years have elapsed since a woman's last tetanus and diphtheria booster, Td is recommended during pregnancy. However, administration of Td may be substituted with Tdap in the immediate postpartum period if sufficient protection from tetanus and diphtheria will be present until delivery. Protection is likely if a pregnant woman has received complete childhood immunization and one or more Td boosters if less than 31 years old or two or more Td boosters if 31 years or older, if the level of serum tetanus antitoxin is 0.1 IU/ml or greater by ELISA.[45]


Typhoid, characterized by fever, gastroenteritis and nonbloody diarrhea, occurs upon ingestion of food or water contaminated with the bacteria Salmonella typhi. Typhoid during pregnancy appears to be associated with a higher incidence of diarrhea as well as other complications such as hepatic dysfunction, gastrointestinal bleeding, intestinal perforation and maternal mortality.[25] Miscarriage, fetal demise and transplacental infection have also been described.

The typhoid vaccine is not contraindicated during pregnancy and women who are anticipating travel to endemic areas (e.g., Latin America, Africa and Asia) should be counseled about vaccination. Several typhoid vaccines are available for use in the USA – an oral live-attenuated vaccine, a parenteral heat-phenol-inactivated vaccine and a parenteral capsular polysaccharide vaccine.[47] Although limited data exist on the safety of these vaccines during pregnancy, use of the capsular vaccine has been recommended by certain experts.[25]


Varicella infection, although uncommon in adults, may result in significant maternal and fetal morbidity. Nearly 30% of pregnant women affected by varicella will succumb to pneumonia.[44] Furthermore, infection during pregnancy may result in congenital varicella syndrome, neonatal varicella or herpes zoster during infancy.[48] Congenital varicella infection may be manifested by cerebral cortical atrophy, microcephaly, low birth weight, cutaneous scaring and limb hypoplasia.

Immunity to varicella should be determined during pregnancy. Evidence of immunity to varicella includes the documentation of age-appropriate vaccination, laboratory evidence of immunity, or verification of a history of varicella or herpes zoster by a healthcare provider.[48] In women who are susceptible to varicella, a two-part vaccination series should be initiated postpartum, with the second dose given 4–8 weeks after the first.[17] Breastfeeding is not a contraindication to vaccination against varicella.[48] As the varicella vaccine is a live-attenuated vaccine, it should not be administered during pregnancy and pregnancy should be delayed for at least 4 weeks after immunization. However, unintentional vaccination during pregnancy is not a reason for termination.


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