Vaccinations in Pregnancy

US Pharm. 2007;32(9):HS-16-HS-26.

Throughout the United States, pharmacists are playing an integral role in educating adults, as well as health care professionals, on the importance of routine adult vaccinations. Despite these efforts, adult immunization rates continue to fall short of national goals set by the CDC because of existing concerns about the safety and benefits of these vaccines.^1,2 Administering routine vaccines during pregnancy heightens these concerns. 

According to the CDC, however, there is no evidence of increased risk to a developing fetus when the mother is vaccinated with inactivated virus or bacterial vaccines or toxoids.^3-5 Health care professionals in all settings should be aware of these issues and discuss them with their pregnant patients. If, after careful consideration, it is determined that a pregnant woman has a high risk of exposure to a disease or the disease could put the mother or fetus at risk, the benefits of vaccine administration should outweigh any possible risks.^6,7 Routine vaccinations considered safe during pregnancy include inactivated influenza, diphtheria, tetanus, and hepatitis B (TABLE 1).

Influenza
Historically, the influenza virus has been responsible for up to 36,000 deaths each year in the U.S.^8,9 The virus classically presents with a fever (101°F-102°F), sore throat, myalgia, and headache lasting two to three days. While the virus can cause disease in all age groups, hospitalizations and deaths from influenza are higher among persons at increased risk for severe complications from infection, including pregnant women^9,10 (TABLE 2). Because of this, the Advisory Committee on Immunization Practices (ACIP) recommends that during flu season, all pregnant women in their second or third trimester be vaccinated with the inactivated influenza vaccine.⁹ Furthermore, pregnant women with concurrent medical conditions (e.g., diabetes, cardiovascular disease, asthma, or immunosuppressive disorders) should receive the flu vaccine regardless of flu season or trimester status. ⁷ Vaccination with inactivated influenza is considered safe for both pregnant women and their fetuses. Two studies involving over 2,250pregnant women found no adverse events after vaccination, regardless of when the vaccine was administered. ^11,12

Tetanus and Diphtheria
While tetanus and diphtheria are rare infections in the U.S. today, cases are still reported each year. The Td toxoid vaccination protects against these two potentially serious infections.

Tetanus infection occurs when Clostridium tetani enters the body through a deep puncture wound or superficial scratch. The bacteria produce a neurotoxin that causes uncontrolled muscle stiffness in the jaw (lockjaw) and neck, followed by generalized rigidity of the skeletal muscles that can lead to respiratory paralysis and death.^6,13,14 While less than 100 cases are reported each year, death rates still approach 25% in unvaccinated individuals or in those who have not received a booster vaccination in the previous 10 years. ^7,15

Diphtheria is an upper respiratory infection that most commonly infects the pharynx and the tonsils but can also present in the larynx and nasal mucosal membranes.^2,16 Once the toxin is absorbed, the bacteria produce an exotoxin that is responsible for life-threatening damage to various organs and tissues away from the site of the original infection. Complications occurring most frequently include neuritis and myocarditis. Fatality rates for individuals not vaccinated against diphtheria are 5% to 10%, with rates approaching 20% in persons younger than 5 years and older than 40 years.¹⁶

The three-dose Td toxoid vaccine, a combination of both the tetanus and diptheria toxoids, is recommended during pregnancy, if indicated. Pregnant women who have been previously vaccinated but have not received a Td vaccination within the last 10 years should receive a booster dose. While no evidence exists that can attribute teratogenicity to the Td vaccination, pregnant women who have not received the initial Td series should not begin until their second trimester as a precaution in order to reduce any concern about the theoretic possibility of adverse reactions.^1,2,6

Hepatitis B
The hepatitis B virus (HBV) is responsible for untoward effects on the liver, including cirrhosis, liver cancer, liver failure, and death.^16,17 Prior to the CDC's recommending the hepatitis B vaccine as a part of routine vaccination schedules for infants in 1991, more than 80% of HBV infections occurred in adults. Today, HBV is uncommon in the general adult population (<20% lifetime risk), with transmission of the infection most likely occurring in unvaccinated individuals who have lifestyles that put them at increased risk for contracting the virus (e.g., heterosexuals with multiple sex partners, intravenous drug users, men who have sex with men, and household contact with a chronic HBV carrier).^2,17 While the incidence of HBV infection has dropped significantly over the past 15 years, implementation of prevention strategies in the adult population is still highly recommended.

Because current hepatitis B vaccines contain noninfectious hepatitis B surface antigen (HBsAg) particles, there is no risk to the fetus when vaccinating for HBV in pregnant women. ^1,2,7 Furthermore, the ACIP strongly urges pregnant women who are at risk for the HBV (e.g., have had more than one sex partner in the past six months, have been evaluated or treated for an STD or recent or current intravenous drug use, or have had an HBsAg-positive sex partner) to receive the hepatitis B vaccine.^1,17

Other Important Vaccines
Several other important vaccines are recommended by the CDC for routine administration in children and adults. While the safety of these vaccines in pregnancy may not be determined, it is imperative that health care providers identify pregnant patients who may be at high risk for exposure to these viruses, weigh the risks and benefits of the vaccine with those of the virus, and carefully consider vaccination in these women. Routine vaccines requiring special consideration for administration in pregnancy include hepatitis A, meningococcal, pneumococcal, polio, and tetanus-diphtheria-pertusis.

In 2006, the CDC recommended the human papillomavirus (HPV) vaccine be a part of the routine vaccination schedule for females ages 9 to 26 years. Safety data on the vaccine's use in pregnancy have not been established. Currently, the quadrivalent HPV vaccine is not recommended for use in pregnancy.¹

Vaccines Contraindicated in Pregnancy
While several routine vaccines have been determined safe for administration during pregnancy, live vaccinations are generally contraindicated because of the theoretical risk of disease transmission to the fetus. It is recommended that women who are accidentally exposed to live vaccines while pregnant or who become pregnant within four weeks of receiving a vaccination be counseled about the possible effects the vaccine may have on the fetus; however, termination of pregnancy is not indicated.² Vaccinations contraindicated during pregnancy include live, attenuated influenza, measles, mumps, rubella, Bacille Calmette-Guerin (BCG), and varicella.

Live, Attenuated Influenza Vaccine: In 2003, a new formulation of the flu vaccine was developed and licensed for use. The live, attenuated influenza vaccine (LAIV) is an intranasal spray that contains the same influenza viruses as the intramuscular injection of the inactivated vaccine. Although the intranasal dosage form may have some advantages, it should not be considered for use in women who are pregnant because of the potential risk the live vaccine may have to the fetus. ^1-3,16 The ACIP recommends that all women who are pregnant during the flu season be vaccinated only with the inactivated form of the influenza vaccine because studies have been done in this population establishing safety and efficacy.^1,2,6

Measles: Measles is a paramyxovirus commonly referred to as the measles virus.¹⁶ It is an extremely contagious disease characterized by a high fever, runny nose, and an erythematous, maculopapular rash on various parts of the body. Other complications associated with the virus include diarrhea, anorexia, and generalized lymphadenopathy.¹⁶ Measles spreads primarily from person to person when noninfected individuals are exposed to infected airborne droplets. Once the virus is airborne, it remains actively contagious for up to two hours.^2,16 While the U.S. recently reported record-low numbers of annual measles cases due to increased vaccination rates, the World Health Organization estimated there have been 30 million cases and more than 450,000 deaths yearly from the disease worldwide.¹⁶

Vaccination against measles is available in combination with mumps and rubella (MMR). Since the measles vaccine is a live, attenuated vaccine, it should not be given to women during pregnancy. Women who have been administered the vaccine are advised not to become pregnant within 28 days of receiving the MMR vaccine or any of its components.^1-3

Mumps: Mumps is an acute viral infection that usually occurs in children but can also present in adults. Mumps is classically characterized by bilateral parotitis, occurring in 30% to 40% of infected people.¹⁶ Other signs and symptoms of the mumps virus include chills, fever, and loss of appetite. Although rare, some severe complications have been known to occur in infected individuals, including testicular inflammation, encephalitis, meningitis, and hearing loss.^2,16

A mumps vaccine is available in combination with MMR. Components of the MMR vaccine are live and attenuated and are therefore contraindicated during pregnancy due to potential adverse effects to the fetus. Women who have been vaccinated against mumps should use some form of contraception for 28 days following the vaccination in order to avoid the theoretical complications associated with vaccination during pregnancy.^2,3

Rubella: Rubella is a highly contagious viral infection characterized by an erythematous rash, low-grade fever, lymphadenopathy, and arthralgia.¹ Rubella is generally considered to be a childhood illness but can occur at any age. Complications associated with rubella infections can range from mild to severe, with the most serious occurring in the elderly population. Congenital rubella syndrome (CRS) occurs when a mother becomes infected with the virus during early pregnancy. Once infected during the first trimester, the mother has an 85% chance of passing the virus on to the fetus.¹⁶ Complications of CRS can result in severe birth defects, including cataracts, mental retardation, hearing loss, heart defects, and even death.^1,2,7,18 Because the rubella virus is extremely rare in the U.S., an independent advisory panel convened by the CDC unanimously determined that rubella was no longer endemic in 2004.¹⁶

The rubella vaccine is available in combination with MMR. Vaccination against rubella is not recommended during pregnancy because of the potential complications the vaccine may have on the fetus. Unvaccinated pregnant women who are susceptible to rubella should receive counseling about the potential complications of CRS and be advised to be vaccinated soon after childbirth.^1,7,16

Bacille Calmette-Guerin: Despite the fact that the disease can be prevented and cured, tuberculosis (TB) remains a significant cause of mortality worldwide, with more than 8 million new cases reported each year. Most cases of TB are found in developing countries where overcrowding and urbanization are common.^2,19 Although reported cases of TB in the U.S. increased in the mid-1980s through 1992, the incidence of TB has currently remained low enough through infectious control practices across the country that it is not recommended as a routine vaccination.^16,19

The BCG vaccine derives from an attenuated strain of Mycobacterium bovis. In the U.S., BCG is recommended for use only in children who are at an inevitable risk of being exposed to untreated or drug-resistant disease.^2,19

The vaccination is not routinely recommended during pregnancy because its safety has not been extensively studied in this population. It is likely that other countries around the world administer the vaccination during pregnancy because no reports are available that can definitively confirm the development of TB in pre- or postnatal infants.^2,20 Despite this, BCG is still not recommended for use during pregnancy.^1,2

Varicella: Varicella, or chickenpox, is a contagious disease caused by the varicella-zoster virus.¹⁹ It presents clinically with a low-grade fever, malaise, and pruritic vesicles that burst, leaving open sores that quickly crust over. Complications such as encephalitis and pneumonia rarely occur but increase in incidence with age.^1,2 Infection by the virus in pregnant women can cause congenital varicella syndrome in the fetus. This complication is characterized by scarring of the skin of the extremities, limb atrophy, microcephaly, cataracts, and other birth defects.^2,21

Vaccination against varicella is contraindicated in pregnant women because of the potential harm the live attenuated vaccine may have on the fetus. Pregnant women inadvertently receiving the varicella vaccine or becoming pregnant within four weeks of vaccination should be alerted to the possible risks to the fetus.^1,7 In addition, if a pregnant woman is exposed to the varicella virus, administration of varicella zoster immune globulin, which contains high titers of the virus antibody and provides passive immunity, is strongly recommended to modify or prevent complications from infection.^1,2

Travel/Other Vaccinations
Some vaccines are not administered on a routine basis but may need to be considered in pregnant women in certain situations. Traveling to countries where various diseases are endemic may require immunizations against those diseases.⁷ When the likelihood of exposure to the virus is high, vaccination benefits will usually outweigh potential risks from the vaccine^1,2,7 (TABLE 3). 

Role of the Pharmacist
The development of vaccines has been a major advancement for global health care. In the United States, the CDC has done a commendable job of increasing the public's awareness of the importance of child and adult vaccinations. Health care professionals are in a position to contribute to the success of national vaccination rates by educating their patients, including pregnant women, on these issues. Practitioners need to take advantage of their unique opportunity to provide mothers with valuable information regarding the risks and benefits of receiving vaccinations versus the risks and benefits associated with the disease during pregnancy. Opportunities for pharmacists to provide pharmaceutical care services are increasing rapidly throughout the country and education and administration of vaccines is high on this list. Whether pharmacies have the resources to administer vaccinations (e.g., a certified pharmacist to administer flu shots, travel vaccinations) or to provide educational information (e.g., handouts about vaccines, recommended immunization schedules), pharmacists can contribute significantly to the improvement of immunization rates among these populations.

References

1. Guidelines for vaccinating pregnant women. Recommendations of the Advisory Committee on Immunization Practices (ACIP). Atlanta, GA: Centers for Disease Control and Prevention; 2007. Available at:  www.cdc.gov/vaccines/pubs/downloads/b_preg_guide.pdf.

2. Sur DK, Wallis DH, O'Connell TX. Vaccinations in pregnancy. Am Fam Physician. 2003;68:E299-E309.

3. Centers for Disease Control and Prevention. General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR. 2006;55 (No. RR-15):1-48.

4. Koren G, Pastuszak A, Ito S. Drugs in pregnancy. N Engl J Med.1998;338:1128-1137.

5. Grabenstein JD. Vaccines and antibodies in relation to pregnancy and lactation. Hosp Pharm. 1999;34:949-960.

6. American Academy of Pediatrics. Immunization in special clinical circumstances. In: Pickering LK, Baker CJ, Long SS, McMillan JA, eds. Red Book: 2006 Report of the Committee on Infectious Disease. 27th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2006:69-71.

7. Tillett J. The use of vaccines in pregnancy. J Perinat Neonat Nurs. 2004;18:216-229.

8. Glezen WP, Greenberg SB, Atmar RL, et al. Impact of respiratory virus infections on persons with chronic underlying conditions. JAMA. 2000;283:499-505.

9. Centers for Disease Control and Prevention. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR. 2006;55 (early release):1-41.

10. Thompson WW, Shay DK, Weintraub E, et al. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA. 2003;289:179-186.

11. Heinonen OP, Shapiro S, Monson RR, et al. Immunization during pregnancy against poliomyelitis and influenza in relation to childhood malignancy. Int J Epidemiol. 1973;2:229-235.

12. Munoz FM, Greisinger AJ, Wehmanen OA, et al. Safety of influenza vaccination during pregnancy. Am J Obstet Gynecol. 2005;192:1098-1106.

13. Wassilak SG, Roper MH, Murphy TV, Orenstein WA. Tetanus toxoid. In: Plotkin S, Orenstein WA, eds. Vaccines . 4th ed. Philadelphia, PA: WB Saunders Co; 2004.

14. CDC. Preventing tetanus, diphtheria, and pertussis among adults: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP) and recommendation of ACIP, supported by the Healthcare Infection Control Practices Advisory Committee (HICPAC), for Use of Tdap Among Health-Care Personnel. MMWR. 2006;55(No. RR-17):1-33.

15. Hackley, BK. Immunizations in pregnancy: a public health perspective. J Nurse Midwifery. 1999;44:106-117.

16. Atkinson W, Hamborsky J, McIntyre, Wolfe S, eds. Epidemiology and Prevention of Vaccine-Preventable Diseases. 10th ed. Centers for Disease Control and Prevention. Washington, DC: Public Health Foundation; 2007.

17. Centers for Disease Control and Prevention. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) part 2: immunization of adults. MMWR. 2006;55(No. RR-16):1-25.

18. Centers for Disease Control and Prevention. Measles, mumps, and rubella: vaccine use and strategies for elimination of measles, rubella, and congenital rubella syndrome and control of mumps: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR. 1998;47(No. RR-8):1-57.

19. Hayney MS. Vaccines, toxoids, and other immunobiologics. In: DiPiro JT, Talbert RL, Yee GC, et al, eds. Pharmacotherapy: A Pathophysiologic Approach. 6th ed. New York, NY: McGraw Hill; 2006:2231-2253.

20. Centers for Disease Control and Prevention. The role of BCG vaccine in the prevention and control of tuberculosis in the United States: a joint statement by the Advisory Council for the Elimination of Tuberculosis and the Advisory Committee on Immunization Practices. MMWR. 1996;45(No. RR-4):1-18.

21. Centers for Disease Control and Prevention. Prevention of varicella: recommendations of the Advisory committee on Immunization Practices (ACIP). MMWR. 1996;45(RR-11):1-25.

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