Toward Optimal Health: A Review of Vaccine Recommendations for Women

Vaccines have been used to induce immunity against diphtheria, polio, pertussis, measles, mumps, and rubella and, more recently, hepatitis A and B, human papillomavirus (HPV), and herpes zoster. Unfounded fears have arisen, however, about the efficacy of vaccines during pregnancy, about a possible link to autism, attention deficit hyperactivity disorder (ADHD), and sudden infant death syndrome (SIDS) in children, and, more recently, about the safety of the newly approved vaccine against the H1N1 flu virus. ¹

Thimerosal-free formulations of the five common childhood immunizations and some versions of Haemophilus influenzae type b (Hib) vaccine have replaced older versions, leading to a reduction in mercury exposure to miniscule amounts, yet lingering fear about exposure to this preservative causes many women to question vaccine safety for themselves and their children. There is little evidence to support the claim that the battery of vaccines given to children can adversely affect their immune system. Experts state that it is not the number of inoculations that matters but the number of immune-stimulating antigens—or proteins—that affect the immune response.

The Centers for Disease Control and Prevention (CDC) recommendation for adult vaccines includes those for herpes zoster, diphtheria, hepatitis A and B, HPV, influenza, measles, meningococcal disease, mumps, pertussis, pneumococcal disease, rubella, and tetanus. Together, these diseases kill more Americans every year than traffic accidents, breast cancer, or HIV/AIDS, according to William Schaffner, M.D., vice president of the National Center for Immunization and Respiratory Diseases, but women still resist the facts and respond with fear.

For all the good that vaccines do, a significant failure in education persists, creating a huge opportunity for better communications by women's health practitioners to make patients aware of adult diseases to which they are vulnerable and of the considerable benefits afforded them by available vaccines. Experts at the CDC review the recommendations and share their insights on the strategies that women's health practitioners can consider to more effectively manage preventable illness caused by known viruses.

Denise J. Jamieson, M.D., M.P.H., is medical officer in the Women's Health and Fertility Branch, Division of Reproductive Health at the CDC, Clinical Professor of Gynecology and Obstetrics, Research Director for Family Planning Fellowship, Department of Gynecology and Obstetrics, Emory University School of Medicine. Rafael Harpaz, M.D., M.P.H., is with the U.S. Public Health Service on the Herpes Virus Team at the National Center for Infectious and Respiratory Diseases/CDC. Lauri E. Markowitz, M.D., is a medical officer at CDC. Jodi Godfrey, M.S., R.D., is a health and wellness specialist in private practice and contributing editor to the Journal.

Given the excessive media attention to the swine flu pandemic, are clinicians adequately informed about the safety and efficacy of the H1N1 vaccine and who should be targeted for immunizations?

Unfortunately, a great deal of misinformation and hesitancy exist among healthcare providers regarding the H1NI vaccine. The fear from the public seems to have sensitized or made many clinicians overly cautious, especially those treating young children and pregnant women, the two most vulnerable target groups. The greatest misperception is that H1N1 vaccine is a “new” vaccine, when in fact the vaccine has not changed; it is simply a strain of circulating virus different from the seasonal types. In fact, the preparation and manufacturing of the flu vaccine remain constant, and each year the vaccine is adjusted to respond to the three most commonly circulating viral strains of influenza.

Among healthy people, the two groups most notably at increased risk of serious illness and hospitalization with influenza infection are healthy women in pregnancy and newborns up to 6 months. Inactivated influenza vaccine has been used in pregnant women since the 1960s in both the United States and Canada; currently, however, only 15% of pregnant women receive the flu vaccine. ² Data from early 2009 H1N1 influenza cases in the United States show that pregnant women account for a disproportionate number of infections (four times more likely to be hospitalized then the general public) and have experienced higher death rates, even among those who were healthy before contracting the virus, making this a high-priority target group for vaccination. ^2,3

Influenza immunization in pregnant women can reduce influenza-like illness by >30% in both mothers and infants and reduce laboratory-proven influenza infections in newborn to 6-month-old infants by 63%. Physicians caring for pregnant women should be aware of the risks of influenza and of the availability of an effective and cost-saving intervention. ⁴ Pregnant women who get swine flu are at high risk of complications, such as dehydration, pneumonia, and premature labor.

Despite the facts, women are still getting mixed messages about the safety of influenza vaccines. A common concern is the presence of thimerosal, a mercury-containing preservative used in some vaccines. It is rarely used, however, and there is no evidence of adverse effects in the very low doses at which it is used even in pregnant women or fetuses. In response to known concerns, the H1N1 vaccine has been produced in two formulations, with and without thimerosal, so women have the option of asking for the thimerosal-free vaccine.

It is important to address the needs of health practitioners with regard to the influenza vaccines. The CDC Advisory Committee on Immunization Practices (ACIP) makes it clear that physicians, emergency medial responders, and allied health professionals should be vaccinated annually against seasonal influenza, ^3,5,6 and healthcare personnel are considered a high priority to receive the H1N1 vaccine. The recommendation goes further to advise that healthcare facilities provide these vaccines to staff as preventive measure as part of a patient safety program. Whereas the CDC recommends that people with influenza-like symptoms remain at home for at least 24 hours after they are free of fever (100° F or 37.8°C), the recommendation for healthcare personnel states that the “exclusion period should be continued for 7 days from symptom onset or until the resolution of symptoms, whichever is longer.”

The CDC has been recommending that all pregnant women be vaccinated against influenza regardless of the trimester, which is a change from the recommendations prior to 2004, which recommended vaccines be given only in the second or third trimester. ⁵ Despite this guidance, only 15% of pregnant women are vaccinated annually. Therefore, health providers must actively encourage patients who are pregnant to be vaccinated and must educate their pregnant patients about the risks faced by not getting vaccinated. Women might feel better knowing that women have been immunized for seasonal flu since the mid 1950s, which is documented in a forthcoming article that summarizes 11 studies published from 1964 to 2008, showing that the influenza vaccine is safe in pregnancy. Also, guidance has been issued for clinicians to promptly treat pregnant women who become infected with the 2009 H1N1 virus with antiviral drugs (www.cdc.gov/h1n1flu/clinician_pregnant.htm). There may be two overriding reasons that preclude pregnant women from getting vaccinated despite the clear benefits to their fetuses. First, obstetricians/gynecologists, unlike pediatricians, have not traditionally offered vaccinations, and these office settings are simply not set up for or geared to giving immunizations. Thus, the H1N1 vaccine is available from pediatricians and state health departments but not from the primary care physicians most likely to treat women who are pregnant. Second, there are barriers (i.e., paper work, tracking systems) to having vaccine programs in many states. Finally, women are likely confused by the availability of vaccines in two formulations, live and attenuated; pregnant women are advised to receive the injectable, inactivated vaccine rather than the live, nasal formulation.

Faced with >1,000 deaths, including a higher than usual number of children and pregnant women, and 20,000 more hospitalized by the virus, based on CDC estimates, President Barack Obama signed a proclamation declaring 2009-H1N1 influenza a national emergency. This proactive move recognizes the possibility of an overburdened healthcare system and creates a temporary waiver of certain standard federal requirements to permit a quicker and wider distribution of the vaccine through emergency operating procedures. The CDC supports the recommendations that the H1N1 monovalent vaccine be made available as broadly as possible, but the policy for distributing and dispensing vaccines is determined on a state by state basis. Given the efficacy profile, clinicians will need to address the reluctance of pregnant women to take any medication including vaccines during pregnancy by becoming more proactive about educating patients about the safety profile of the vaccine and the risks of not getting vaccinated.

The seasonal trivalent flu vaccine immunizes against the three strains of influenza that are most prominently circulating. The reason H1N1 is not included in the seasonal vaccine is that it arose too late to be incorporated into the seasonal vaccine this year. Had it been, there probably would have been much less fuss surrounding its safety. Both vaccines can be given at the same time; the only caveat is that it is strongly recommended that the vaccines be given at two different sites, such as one in each arm, to reduce any discomfort from a local reaction.

Should women who develop flu-like symptoms be tested to determine the causative virus, and what treatment options should clinicians recommend for either seasonal or H1N1 influenza?

It is worth noting that the overwhelming volume of cases has pushed the testing capacity at state laboratories to their limit because of the H1N1 pandemic, and the chance of a quick confirmation is unlikely. As the vast majority of current influenza cases are attributable to the H1N1 strain, it is presumed to be the most likely cause of symptoms. More importantly, the treatment for influenza is the same regardless of the strain producing the illness. In the Southern Hemisphere, the seasonal flu has peaked, and the dominant strain of influenza was H1N1. Although we cannot predict the spread of the influenza virus in North America, CDC anticipates H1N1 will predominate here. Given that cases began to appear in the United States in April and have already peaked at many colleges in the south, the expected trend is H1N1 being the predominant influenza moving north in the coming months.

Any woman, particularly if she is pregnant, who develops flu-like symptoms should contact her primary care provider as soon as possible to receive prompt antiviral therapy. Oseltamivir (Tamiflu, Roche Pharmaceuticals, Nutley, NJ) is approved as first-line therapy for influenza for anyone over age 1, including pregnant women. Antiviral therapy is most effective when delivered within the first 48 hours of onset of symptoms. However, it should be prescribed as soon as possible even if the patient has symptoms beyond the ideal treatment phase. Zanamivir (Relenza, GlaxoSmithKline, Research Triange Park, NC) is FDA approved for anyone over age 7. These two FDA-approved influenza antiviral drugs are recommended by CDC for use against both the 2009 H1N1 influenza virus and seasonal flu virus. Tamiflu is not normally recommended for use by pregnant women because the effects on the fetus are unknown, but this should not be construed as confirming risk. Instead, it points to the lack of sufficient safety data because clinical trials are not typically done in pregnant women or infants. Tamiflu and Relenza are in the same class of drugs. Because Tamiflu is available in both pill and liquid form and Relenza is a powder that must be inhaled, Tamiflu remains the antiviral of choice.

As of October 23, 2009, the FDA authorized emergency use of the investigational antiviral drug peramivir intravenous (IV) (BioCryst Pharmaceuticals, Durham, NC) in adult and pediatric patients with confirmed or suspected H1N1 influenza infection who are admitted to a hospital and do not respond to either oral or inhaled antiviral therapy, when other drug delivery routes are not advised, and for adults as deemed clinically appropriate.

For adult women who have had all their childhood vaccines, are there vaccines they should consider as adults?

The CDC recommends that in addition to influenza, women be vaccinated against chickenpox, diphtheria, hepatitis A and B, HPV, measles, meningococcal disease, mumps, pertussis, pneumococcal disease, rubella, zoster, and tetanus. ^7,8 The quadrivalent HPV vaccine was recommended exclusively for females when first licensed in 2006 and provides protection against HPV infection; cervical, vaginal, and vulvar cancers; and genital warts caused by HPV types 6, 11, 16, and 18. It is approved for use in girls and young women aged 9–26. ^9,10 New research is underway on the safety and efficacy of the HPV vaccine in women older than 26. The current recommendation focuses on girls 11 and 12 (although vaccinating girls aged 9 and 10 is acceptable), with a catchup through age 26 years for women who have not yet received the vaccine.

The findings of adverse events after HPV vaccination are similar to the safety reviews of other vaccines recommended for a similar age group, 9–26 years old (meningitis and tetanus-diphtheria-acellular pertussis [Tdap]), and its benefits continue to far outweigh any risks. ¹² Since approval of the HPV vaccine, the vast majority (94%) of adverse events have been minor, with the most common being syncope (common after needle injections, especially in preteens and teens). ¹² To date, an estimated 37% of 13–17-year-olds and 9% of 18–26-year-olds have been vaccinated for HPV. Knowledge about HPV varied, with no more than 5% subjects appreciating the need for continued Pap smears and safer sex practices. ¹³ Requests for the vaccine are most common among girls after a healthcare visit and more common among 18–26-year-olds who discuss the HPV vaccine with a family member or a healthcare provider. ¹⁴ A majority of parents, teens, and young women want the vaccine and perceive it to be important to their health, according to data collected in California. ¹⁵

The Food and Drug Administration (FDA) will review data on the HPV vaccine in women >age 26 within the next year. A bivalent HPV vaccine with slightly different characteristics was licensed in October 2009. Although the bivalent vaccine does not protect against the two HPV types that cause genital warts, data suggest the vaccine may confer protection beyond oncogenic types 16 and 18.

What recent developments regarding vaccines may have particular relevance to women?

According to physicians, including internists, geriatricians, and family practitioners, in patient care settings, few of their older patients know the symptoms of zoster (shingles), and there is a clear need to educate the public about the disease. ¹⁶ More than 60% of primary care physicians surveyed at a recent meeting of the American Academy of Family Physicians indicated difficulty treating patients with shingles. ¹⁶ Women do not realize that if they had chickenpox as a child, they are at risk for developing shingles as an adult. Even more troublesome is that many woman believe they never had chickenpox, even though >90% of Americans >age 15 have had it. ¹¹ It seems to be one of those occurrences that does not leave a lasting memory. Chickenpox infection in childhood may lead to shingles in later adulthood as a result of reactivation of the herpes zoster virus in the dorsal root ganglia. Shingles characteristically causes a painful, debilitating rash with a unilateral dermatomal distribution that usually resolves within 2–4 weeks. For some, the pain persists for months or even years and is termed postherpetic neuralgia (PHN). ^11,17

The frequency of shingles is near constant between 20 and 50 years (2.5 cases per 1000 people per year). ¹¹ The chance of getting shingles doubles from 50 to 60 years of age and doubles again in the next decade. Shingles vaccine is recommended by the ACIP to reduce the risk of shingles and its associated pain in people ≥60 years old. ¹¹ Shingles vaccine is not recommended for use in pregnant women, which is not a concern because these women are not in the vaccine target age group.

Strategies to promote shingles vaccination include linking delivery of shingles vaccine to that of other indicated adult vaccines (e.g., influenza) and preventive health interventions, standing orders so that patients will automatically be offered indicated vaccines rather than requiring case by case physicians' orders, and practice-based audits or physician reminder systems.

It is better to immunize women with most vaccines before they are pregnant in order to also protect the fetus from infection and its complications, which suggests a stepped-up effort to encourage vaccinations before conception. Women who have never had chickenpox can avoid contracting the virus that causes both chickenpox and shingles by receiving the herpes zoster vaccine. Similarly, the adult and adolescent 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. Rubella is another vaccine for adult women to consider. ⁸ Several vaccine safety issues of particular relevance to women include the theoretical risk of administering live vaccines during pregnancy and data suggesting that adolescent females might be at higher risk for syncope after vaccination. ⁸

Especially serious diseases for women aged ≥65 include diphtheria, pneumococcal disease, and tetanus. Obstetrician gynecologists may be the primary, and sometimes only, contact with the healthcare system for many adolescent and adult women, and it may fall to them to address the need for vaccinations. Unfortunately, such issues as storage and handling requirements, lack of access to immunization information systems and vaccine registries, and unfamiliarity with current recommendations are potential obstacles to ensuring that all adolescent females and women are appropriately vaccinated. ⁹ Obstetrician/gynecologists can help reduce some of these obstacles by availing themselves of existing vaccination resources.

Which vaccines are contraindicated during pregnancy, and which are to be encouraged by clinicians?

Rates of seasonal influenza among women vaccinated during pregnancy and among their infants are virtually the same as illness rates among women who had not been vaccinated during pregnancy and among their infants. ⁶ However, the rates of serious, even fatal, reaction to the H1N1 influenza strain have been four times greater than in the general population, providing a strong rationale for placing pregnant women and infants <6 months at the top of the priority list to receive the monovalent H1N1 vaccine as well as the seasonal influenza vaccine. The introduction of live attenuated influenza vaccine, which is delivered in a nasal spray, added to the confusion about the safety of flu vaccination during pregnancy, necessitating effective communication by physicians seeing pregnant women as well as those considering pregnancy in the near future. Overall, the benefits of vaccination outweigh any potential risks, particularly with regard to the H1N1 influenza vaccine. Most compelling is the fact the vaccinating late in pregnancy provides protection not only for the woman but also for the newborn. ⁶

As discussed, the herpes zoster and measles, mumps, and rubella vaccines are contraindicated during pregnancy, whereas pneumococcal, hepatitis A, hepatitis B, and meningococcal vaccines are recommended during pregnancy when other risk factors are present.