Abstract
Recommendations for routine vaccination of adolescents and adults are continually evolving; new vaccines are licensed, and ongoing studies lead to updated recommendations for existing vaccines. Although vaccination is important for both sexes, some recent developments are particularly relevant for women and girls. Human papillomavirus (HPV) vaccine, licensed in 2006, is the first vaccine administered exclusively to women. Another recently licensed vaccine, adult and adolescent tetanus-diphtheria-acellular pertussis (Tdap), is especially important for women who plan to become pregnant and for new mothers to help prevent pertussis disease in infants who are too young to be vaccinated themselves. Other vaccines, such as influenza and rubella, are also important for pregnant women. Several vaccine safety issues are of particular relevance to women, namely, the theoretical risk of administering live vaccines during pregnancy and data suggesting that adolescent females might be at higher risk for syncope following vaccination. Obstetrician-gynecologists are the primary, and sometimes only, contact with the healthcare system for many adolescent and adult women and, as such, are uniquely positioned to provide vaccination services to the country's female population. Vaccine costs, storage and handling requirements, lack of access to immunization information systems (also known as vaccine registries), and unfamiliarity with current recommendations are potential obstacles to ensuring that all adolescent females and women are appropriately vaccinated. Obstetrician-gynecologists can help reduce some of these obstacles by availing themselves of existing vaccination resources.
Introduction
In 2004,
In this report, we describe updates to the routine adolescent and adult immunization schedules and discuss vaccinations that are of special interest to women. Human papillomavirus (HPV) vaccine was licensed in 2006 and at this time is recommended exclusively for women. The first pertussis-containing vaccines for adolescents and adults (tetanus-diphtheria-acellular pertussis, or Tdap) were licensed in 2005, and recommendations for use of these vaccines among pregnant and postpartum women were published in 2008. Several other vaccines are important for pregnant women and women in general. We discuss these vaccines, summarize key information on vaccine safety and efficacy, and touch on several programmatic issues (e.g., vaccine financing, vaccine storage and handling, use of vaccine information statements, and reporting of adverse events and administration errors). Obstetrician-gynecologists are the primary contact with the healthcare system for many adolescent and adult women and are the main audience for this report.
Vaccines Important for Women
Vaccine exclusively for women: Human papillomavirus
Genital HPV is the most common sexually transmitted infection (STI) in the United States, causing approximately 6.2 million new infections each year. 2 Almost 100% of cervical cancers can be attributed to HPV infection. 3,4 Worldwide, cervical cancer is the second or third leading cause of cancer deaths among women, 5 and it is estimated that HPV infection is responsible for at least 250,000 deaths from cervical cancer each year. Most of these occur in the developing world, but about 3,700 occur in the United States. 6 HPV infection has also been associated with cancer of the anus, vulva, vagina, penis, oral cavity, and pharynx and with anogenital warts in both women and men. 6
In 2006, an HPV vaccine, marketed as Gardasil® (Merck & Co., Rahway, NJ), was licensed for females 9–26 years of age. (A second HPV vaccine is pending licensure as this is being written.) Gardasil vaccine contains 4 of approximately 100 HPV types, including 2 types that cause about 70% of cervical cancer and 2 types that cause about 90% of anogenital warts. About three fourths of HPV infections occur between the ages 15 and 24 years, and the first infection generally occurs soon after onset of sexual activity. 6 For this reason, it is important to vaccinate girls before they become sexually active. This has caused controversy among some parents and groups who resist vaccinating young girls against an STI for which they may not yet be at risk. However, vaccination prior to exposure can provide virtually 100% protection against infection with the 4 types of HPV virus contained in the vaccine. Once a person has been infected with a type of the virus, the vaccine does not provide protection against progression to disease, but it will still provide protection against the other 3 types. Whereas there are treatments for disease due to HPV, there is no cure for HPV infection. This makes prevention through vaccination even more important. Routine cervical cancer screening, including Pap smears, should still be conducted for females who have received HPV vaccine. The recommended schedule for HPV vaccine is three doses, with the first dose administered at 11 or 12 years of age, the second dose 2 months after the first, and the third dose 6 months after the first. (Links to routine immunization schedules for adolescents and adults can be found in Table 1.)
CDC, Centers for Disease Control and Prevention; VAERS, Vaccine Adverse Event Reporting System; VIS, Vaccine Information Statement; ACOG, American College of Obstetricians and Gynecologists.
Girls as young as 9 years may be vaccinated. Healthcare providers can promote the use of HPV vaccine in the older adolescent population. Catchup vaccination is recommended for females 13–26 years of age, and the series need not be restarted if there is a lapse in the schedule. As with all vaccines, HPV vaccine may be given at the same visit with other age-appropriate vaccines.
Pregnant women should not receive HPV vaccine. Although the vaccine has not been associated with adverse pregnancy outcomes or harm to the fetus, vaccination during pregnancy has not been thoroughly studied. The vaccine series may be initiated after completion of the pregnancy; if a woman becomes pregnant after starting the series, the remaining doses should be delayed until after delivery.
Males are also subject to HPV infection, and licensure of HPV vaccine for males has been applied for. For more information about HPV and HPV vaccine, see the Advisory Committee on Immunization Practices (ACIP) recommendations. 6
Vaccines and pregnancy
Several vaccines are of particular importance for pregnant women or, more broadly, for women of childbearing age, to protect both the women themselves and their unborn offspring. As a general rule, inactivated vaccines may be administered to pregnant women when indicated, and live vaccines should be deferred. 7 Table 2 provides information about specific vaccines for pregnant and postpartum women. No currently recommended vaccines are contraindicated for nursing mothers. Three vaccines that are especially relevant in relation to pregnancy are influenza, rubella, and Tdap.
See recommendations for individual vaccines. Some vaccines should be considered only after risk/benefit analysis.
HPV, human papillomavirus; TIV, trivalent influenza vaccine; LAIV, live attenuated influenza vaccine; MMR, measles, mumps, rubella vaccine; MCV4, meningococcal conjugate vaccine, quadravalent; MPSV4, meningococcal polysaccharide vaccine, quadravalent; PPSV23, pneumococcal polysaccharide vaccine, 23-valent; Td, tetanus-diphtheria toxoids; Tdap, tetanus-diphtheria toxoids, acellular pertussis vaccine; BCG: bacillus of Calmette and Guérin (tuberculosis) vaccine.
If susceptible to rubella.
Td preferred over Tdap for pregnant women not at high risk for pertussis.
Women of childbearing age who have received at least one dose of live rubella vaccine (usually as part of the combination measles-mumps-rubella [MMR] vaccine) or those who have had rubella disease can be considered immune. Other women of childbearing age should be vaccinated with MMR. Because of the critical importance of protecting women of childbearing age against rubella, opportunities for vaccination should be widespread. They can include vaccinating in family planning clinics, STI clinics, and as part of routine gynecological care; emphasizing immunization for college students; immunizing prison staff and, when possible, inmates; offering vaccination through the Women, Infants and Children (WIC) program; and implementing vaccination programs in the workplace.
A woman who is already pregnant or who expects to become pregnant within 4 weeks should not receive MMR vaccine. A woman who has received the vaccine should wait at least 4 weeks before becoming pregnant. These precautions are based on a theoretical risk to the fetus from the live vaccine. During the 1970s and 1980s, CDC maintained a registry of women who were inadvertently vaccinated during pregnancy, and none of the children of these mothers developed CRS. Women who are inadvertently vaccinated while pregnant or who become pregnant within 4 weeks of vaccination should be counseled about the theoretical risk, but MMR vaccination during pregnancy should not ordinarily be a reason to consider termination of the pregnancy. Pregnant women known to be susceptible to rubella should be vaccinated immediately postpartum. 9
The ACIP does not recommend
While data about its safety and efficacy are insufficient to recommend Tdap for pregnant women, there is also no evidence showing that it would be harmful to the fetus or would cause adverse pregnancy outcomes. Some evidence suggests that antibodies to pertussis passed transplacentally from a recently vaccinated woman to her infant could interfere with the baby's response to the pertussis component of pediatric diphtheria, tetanus, acellular pertussis (DTaP) vaccine. 10 Because of the critical importance of preventing pertussis in infants, however, studies are underway to determine if a pregnancy dose should be given. Pregnant women needing immediate protection against tetanus or diphtheria should usually receive Td vaccine, although Tdap is not strictly contraindicated and may be given in special situations after an informed discussion with a doctor; for example, if the woman is at increased risk for pertussis during an outbreak.
For pregnant women who have never received Tdap vaccine, a dose is recommended as soon after delivery as feasible—ideally before discharge—to protect the women from pertussis and reduce the risk for exposing their infants to pertussis. 10 An interval of 2 years from the previous dose of Td is suggested, but shorter intervals are acceptable. A history of pertussis disease is not a reason to defer this dose. 10
Women who are susceptible to varicella (chickenpox) should receive a dose of
Pregnancy registries exist to track pregnant women who are inadvertently vaccinated with Tdap, HPV, or varicella vaccines. Call 1-(800)-986-8999 (HPV or varicella vaccine), 1-(800)-822-2463 (Sanofi Pasteur's Tdap vaccine), or 1-(888)-825-5249 (GlaxoSmithKline's Tdap vaccine) for information about these registries.
Vaccines for Adolescents and Adults in General
In addition to the vaccines described, which are particularly important for women, several other vaccines are recommended for adolescents and adults of either sex. Other vaccinations that women should consider, depending on age, circumstances, and contraindications or precautions, include meningococcal, hepatitis A, hepatitis B, pneumococcal, MMR, varicella, and zoster (shingles) vaccines.
One dose of
A three-dose series of
A dose of
All adolescent and adult women who are not pregnant should receive
One dose of
In addition to these relatively common vaccines, other vaccines, such as those for typhoid, yellow fever, Japanese encephalitis, or rabies, may be indicated for international travelers. CDC's Travelers' Health website (
Vaccine Safety
Vaccine safety concerns are not new; since vaccines were first developed, the public has been concerned about their safety. Vaccine manufacturers and immunization providers are also concerned about the safety of vaccines. A higher standard of safety is expected of vaccines than of other medications because, unlike other pharmaceutical products that are administered to ill persons, vaccines are generally given to healthy individuals. 7 Maintaining the public's trust in vaccines is crucial in preventing a decline in vaccination rates, which could then lead to outbreaks of disease. 7
Like any other medical product, no vaccine is 100% safe or effective. Before being licensed, vaccines undergo extensive safety and efficacy studies. These safety studies are conducted in the laboratory, in animals, and in humans. Prelicensure human studies consist of phase I, II, and III trials, involving progressively more participants, and are designed to detect common serious side effects and to determine the most effective use of the vaccine, the best dose for effectiveness and safety, and the optimum number of doses. 7 Trials are terminated for vaccines found to have serious side effects.
The comparatively small number of patients enrolled in prelicensure trials (generally thousands) limits detection of rare side effects or adverse events that may occur months after the vaccine is received. Therefore, postmarketing surveillance of the vaccine is continual. This is done primarily through the use of reporting systems, such as the Vaccine Adverse Event Reporting System (VAERS), as well as by large-linked patient databases, such as the Vaccine Safety Datalink (VSD). These postlicensure safety activities not only identify rare adverse events but also are used to monitor increases in known reactions, identify risk factors for reactions, identify vaccine lots associated with unusual rates or types of events, and identify signals of possible adverse reactions that may warrant further study or affect current immunization recommendations. 7
VAERS is a collaboration between CDC and the Food and Drug Administration (FDA). It is a passive reporting system whereby healthcare providers, vaccine manufacturers, and the general public can report any clinically significant adverse event that occurs following administration of a licensed vaccine. VAERS collects and analyzes this information to detect any new or rare events (signals) or increases in rates of known side effects or patient risk factors following a particular vaccine. All reports are confidential. A major limitation of VAERS is that the system cannot distinguish between adverse events causally associated with vaccination and those that are coincidental. Additional studies, such as those conducted using the VSD, are required to determine whether or not signals generated by VAERS represent events causally related to vaccines. 20
Since 2005, an increase in the number of reports of syncope following vaccination has been detected by VAERS. Most of this increase has been seen among females 11–18 years of age, many of whom have received HPV, Tdap, or quadravalent meningococcal conjugate (MCV4) vaccine. Rarely, serious head and other bodily injuries have resulted from falls associated with syncope. The greater number of vaccines that adolescents now receive at one visit, rather than a specific risk associated with a single vaccine, may account for the increased reports of syncope to VAERS. 21 The ACIP and CDC recommend observing vaccine recipients for 15 minutes after they receive any vaccine.
Programmatic Concerns
The majority of obstetrician-gynecologists and family practitioners serve both adolescents and adults. 22 Some studies have shown that older adolescents make more outpatient visits to family practice physicians and internists. Thirty-five percent of preventive visits made by older adolescent females aged 18–21 years (for well-adolescent care, not prenatal care) were to obstetrician-gynecologists. 23 Obstetrician-gynecologists are the first and most frequent point of contact for young women who seek medical consultation for reproductive health and are primary caregivers for many nonpregnant women who have little or no other contact with the healthcare system. 22 The American College of Obstetricians and Gynecologists (ACOG) recommends that the first visit to an obstetrician-gynecologist should take place between 13 and 15 years of age to receive screening and preventive healthcare services and guidance. 24 Obstetrician-gynecologists provide more office-based, general medical examinations to women aged ≥15 years of age than do either family practice or internal medicine specialists. 25 However, other studies have shown that younger adolescents ≤14 years primarily visit pediatricians for both overall care and preventive visits. 23 Results of the study by Rand et al. 23 show that adolescents typically received immunizations at preventive visits and rarely during visits to obstetrician-gynecologists or subspecialities. This presents a greater challenge to obstetrician-gynecologists to offer vaccinations to their adolescent patients at all visits, particularly acute care visits, as they may not see the adolescent for their preventive care visit.
Despite the apparent suitability of obstetrician-gynecologists, family practitioners, internists, and pediatricians as immunization providers, several programmatic issues affect their ability or willingness to provide more widespread vaccination services. These include issues related to vaccine financing, vaccine storage and handling, and educational resources for vaccine providers. During the last 5 years, several new vaccines have been added to both the childhood/adolescent and the adult immunization schedules. The high cost of these vaccines could lead to delays in their adoption because of concerns about reimbursement for both the vaccine cost itself and the cost of administration. This has been studied mainly with childhood vaccines. One study indicated that about half of the 784 family practitioners and pediatricians who responded to a survey in 2007 reported their practice had “delayed the purchase of specific vaccines for financial reasons” during the previous 3 years. The vaccines most commonly cited for delayed purchase were HPV and MCV4 because of high vaccine inventory costs and varying levels of insurance reimbursement. 26,27
Similar concerns are expressed by obstetrician-gynecologists. In a survey mailed to ACOG members in 2001, 593 members who responded reported that the two most common reasons for not offering vaccines were cost (44%) and a belief that vaccines should be provided elsewhere (41%). 28 Attitudes may have changed since the introduction of the HPV vaccine and the sense by obstetrician-gynecologists of the importance of this vaccine.
The total cost of immunizing patients comprises much more than the purchase cost of vaccines. Additional costs include administrative and staffing expenses related to ordering and inventory control of vaccines and the cost to insure vaccine supply. Equipment required for vaccine storage, such as refrigerators and backup generators, must also be considered, as must vaccine wastage. Also, the interval between the time vaccines are purchased and the time their cost is recouped through payment from insurance carriers needs to be considered. 29 Indeed, lack of adequate vaccine storage and handling has been cited as a barrier to vaccination. 28 CDC's Vaccine Storage and Handling Toolkit provides practical information on storage and handling of vaccines and information on how to protect the vaccine supply (Table 1).
Another hindrance to providing immunizations is the lack of access to electronic immunization information systems (IIS, also called vaccine registries) by obstetrician-gynecologists. The ability of a provider to access a patient's vaccination history and to document vaccinations administered (particularly for adolescent patients) will result in fewer missed opportunities to vaccinate and prevent repetition of vaccinations previously administered. IIS should be made available to all providers and obstetrician-gynecologists, and these groups should be encouraged to participate in these systems.
Interventions shown to improve adult vaccination coverage in a variety of provider settings 30 should be disseminated more widely as well as tested specifically in obstetrics-gynecology practice settings. These include the use of standing orders—protocols whereby nonphysician medical personnel can prescribe or deliver vaccines to patients without direct physician involvement at the time of interaction. 30 Increasing awareness among the adult population of what vaccines are recommended for their age and circumstances is also essential. This information needs to be communicated to adults by healthcare providers. 31,32 Offering vaccines in nontraditional settings (e.g., pharmacies and churches) has also been shown to be effective. 31 Support and further recommendations from ACOG will be key in determining whether obstetrician-gynecologists adopt immunization services as part of their routine scope of care and offer vaccinations to their clients. 22
Resources
Providing access to educational tools related to vaccination was cited in one survey of ACOG members as a means to increase vaccine administration in obstetric-gynecology practices. 28 Numerous resources are available through CDC, FDA, and the Immunization Action Coalition (IAC) that can provide obstetrician-gynecologists with the tools needed to deliver vaccines in an efficient and safe manner in their offices (Table 1). Another useful resource is a web-based training module developed by CDC, titled “The Immunization Encounter: Critical Issues” (Table 1). This webcast is designed to educate immunization providers on all aspects of the immunization clinic encounter, including patient intake and screening, vaccine administration, vaccine management, documentation, vaccine adverse events management and reporting, and resources for staff orientation and development. It also provides practical tips for avoiding common vaccine administration errors, including those involving needle length, administration site, and use of the appropriate vaccine diluent. Also addressed is the use of Vaccine Information Statements (VISs), one-page information sheets required by federal law to inform patients about the risks and benefits of vaccines they are receiving. VISs can be downloaded in English and many other languages from the CDC website (Table 1).
Anaphylaxis following vaccination occurs only rarely, but being prepared for such emergencies by ensuring that appropriate equipment and guidelines are available if they do occur is essential. Emergency protocols for vaccine reactions can be found in Appendix D of Epidemiology and Prevention of Vaccine-Preventable Diseases. 7
Two CDC publications provide a wealth of practical information for offices where vaccinations are provided. The first is the ACIP's General Recommendations on Immunization, 33 which spells out the ACIP's recommendations on the essential theory and practice of immunization, from timing and spacing of vaccine doses, to distinguishing true contraindications from common misperceptions, to vaccine recommendations for immunocompromised patients, to identifying administration errors. The second is CDC's textbook, Epidemiology and Prevention of Vaccine-Preventable Diseases (the Pink Book), which condenses ACIP recommendations on all routine vaccines into a single user-friendly volume. 7
Information about reporting reactions after immunization is available online at
Conclusions
The purpose of this report is to provide updated information on vaccines that are important for women, including pregnant women and adolescent females; to update current vaccine safety concerns and programmatic issues relevant to obstetrician-gynecologists who deliver vaccines; and to suggest helpful resources and tools.
Educating women about the benefits and risks of vaccination clearly and concisely will help address concerns among the public about the safety of vaccination. Even obstetrician-gynecologists who do not administer vaccines can counsel patients about the known benefits and risks of vaccination while stressing benefits not just to the patients themselves but also to their children, both unborn and living. 34 Because women often assume the responsibility for their entire family's health as well as their own, anything we as health professionals can do to ensure that they are well informed about vaccination for their families, and are appropriately vaccinated themselves, can enhance vaccine coverage and, hence, improve the nation's health by limiting preventable morbidity and mortality from vaccine-preventable diseases.
