Which female patient would the nurse exclude when providing rubella immunizations

Practice Essentials

An essential component of preventative health care, immunization reduces the incidence and severity of vaccine-preventable diseases. [1] Pregnant women and neonates are particularly vulnerable to infectious disease due to altered and underdeveloped immune responses. Vaccination in pregnancy provides maternal protection through active immunization, while passive maternal antibody transfer across the placenta to the developing fetus has the potential to protect neonates and infants. [2]  In 2008, the Advisory Committee on Immunization Practices (ACIP) established general principles on the immunization of pregnant and breastfeeding women and cited the following rationale for maternal immunizations: (a) to protect the mother, (b) to protect the fetus, (c) to protect the neonate, or (d) to protect the young infant. [3]  Growing evidence on the safety and efficacy of influenza and tetanus, diphtheria, and pertussis (Tdap) immunizations in pregnancy has highlighted maternal immunization as an important strategy to reduce morbidity and mortality in women and newborns. [4, 5, 6, 7, 8]

All women, including women of reproductive age, should have their immunization history and eligibility assessed to ensure they have been immunized according to current Centers for Disease Control (CDC) adult immunization schedules, which are approved yearly by the ACIP. [1, 9]  Although recommended routine adult immunizations are ideally administered prior to pregnancy, pregnant women should receive appropriate vaccines as indicated by age or risk factor. A caution is that some vaccines are contraindicated in pregnancy. Two vaccines are routinely recommended in pregnancy: influenza vaccine and the combined Tetanus, Diphtheria, and Pertussis (Tdap) vaccine.

This article reviews CDC and ACIP recommendations for immunizations routinely recommended in the United States (US) before, during and after pregnancy, as well as those indicated in special situations. Immunizations contraindicated in pregnancy and considerations during breastfeeding are also reviewed. Table 1 provides an overview of CDC and ACIP recommendations for maternal immunization.

For a complete list of recommended adult immunizations, please see the CDC adult immunization schedules.  

Influenza

Influenza and Pregnancy Outcomes

Pregnant women are at increased risk for severe complications from influenza infection as compared with non-pregnant women and the general population. [10, 11, 12]  Changes to immune and cardiorespiratory systems in pregnancy increase susceptibility for certain infections and place women at risk for influenza-associated complications. [13, 14]  During both seasonal influenza epidemics and pandemic influenza outbreaks pregnant women have greater rates of hospitalization, admission to intensive care units and higher mortality than both non-pregnant women of reproductive age and the general population. [12]   

Seasonal influenza results in greater hospitalization rates for pregnant women, suggesting increased disease severity. Studies have demonstrated that pregnant women were more likely to be hospitalized for acute cardiorespiratory illness during flu season compared with recently post-partum women [15] , and that the proportion of pregnant women hospitalized with respiratory illness is greater during influenza season. [16]  Hospitalization rates due to influenza-associated complications are highest for women in their second and third trimester and for women with comorbidities. [17]  While seasonal influenza poses an increased risk for all pregnant women, severity of disease increases with each trimester and is greatest for women with medical comorbidities.

Pandemic influenza led to increased maternal morbidity and mortality during the pandemics of 1918, 1957 and, most recently, 2009. [18, 19, 20]  Pregnant women were more than four times as likely to be hospitalized with laboratory-confirmed influenza virus in 2009 compared with the general population, and though pregnant women represent only 1% of the U.S. population, they accounted for 5.9% of ICU admissions and 5.7% of deaths associated with the 2009 H1N1 influenza virus. [21, 22]  Similar to seasonal influenza, morbidity and mortality was highest among women in their second or third trimester; however, severe illness resulting in ICU admission or death occurred in all trimesters. [19, 23]

Influenza and Infant Outcomes

Influenza virus is a significant risk for newborns and infants due to their incompletely developed immune systems. While studies are inconclusive on the impact of maternal influenza virus on fetal and neonatal outcomes, infants under 6 months have higher rates of hospitalization and increased mortality associated with influenza infection relative to infants greater than 6 months and children in other age groups. [24, 25, 26]  The higher rate of morbidity and mortality is important to note in the context of maternal immunization because infants less than 6 months of age are not eligible for preventive influenza vaccine and infants less than 2 weeks of age are not eligible for antiviral medications such as oseltamivir.

Among children under 5 years of age, infants less than 6 months face the highest burden of disease from complications of influenza. Available data from the seasonal flu in 2002-2003, 2003-2004 and a retrospective review of hospitalization rates for seasonal influenza from 2003-2008 noted the highest risk of hospitalization for infants less than 6 months among all children 0-59 months. [24, 25]  This age group also has the highest rates of mortality from seasonal flu. [26]  Data on pandemic flu are more limited, however, a study from the H1N1 outbreak in California found that similar to seasonal flu, a greater proportion of infants under 6 months were hospitalized with influenza complications than those older than 6 months. [27]

The impact of maternal influenza disease on fetal and neonatal outcomes remain unclear, with some studies finding that newborns of mothers hospitalized for respiratory illness during the flu season (a proxy for influenza disease) were more likely to be small for gestational age and low birth weight while other studies have found no difference in neonatal outcomes by maternal hospitalization for acute respiratory illness. [19, 28, 29]  In contrast, the 2009 H1N1 pandemic influenza epidemic led to an increase in adverse pregnancy outcomes among hospitalized women with a diagnosis of H1N1, including increased rates of preterm birth and stillbirths and a lower mean birth weight. Risk factors for these adverse outcomes included influenza infection while in the third trimester, admission to the ICU, and pneumonia. [30]  Other studies have identified similar increases in spontaneous abortion and preterm birth following pandemic influenza infection. [31, 32, 20]

A few studies have suggested an association with maternal influenza illness and congenital anomalies, particularly cleft lip, neural tube defects and cardiac defects; however, these reports are inconclusive. [33]  Fetal anomalies have been associated with maternal fever, particularly high fevers that occur in the first trimester during organogenesis. As influenza infection is often accompanied by fever, it is possible that anomalies associated with influenza illness were the result of maternal fever and not specific to influenza infection. [34]  Women with fever in pregnancy should be treated with acetaminophen to reduce core body temperature and minimize fetal risks.

Poor infant outcomes reflect the limited options available for the youngest age group for both treatment and chemoprophylaxis. Neuraminidase inhibitors, antiviral medications approved for the prevention and treatment of influenza virus, are not FDA-approved for use in infants under 2 weeks of age. Due to the underdeveloped immune system in infants, the influenza vaccine is not approved for infants less than 6 months. To protect this age group through passive immunization and decreased exposure, the CDC and the American College of Obstetricians and Gynecologists (ACOG) recommend a combined strategy of immunization in pregnancy and vaccination of all household members and caregivers. [12, 35, 36]

Rationale for Influenza Vaccination

The inactivated influenza vaccine is recommended for all pregnant women in all trimesters. Influenza vaccination has the same efficacy in pregnant women as in the general adult population and reduces rates of influenza illness, influenza-related hospitalization, and the severity of influenza complications. [12, 37]

Multiple studies have demonstrated reductions in adverse pregnancy outcomes, neonatal outcomes and infant morbidity and mortality after maternal influenza vaccination during pregnancy. A retrospective US study from the state of Georgia noted reductions in preterm delivery and small for gestational age infants among women who had documented influenza immunization during pregnancy. [38]  Notably, a large randomized control trial in Bangladesh found that maternal immunization reduced influenza-like illnesses (ILI) by 63% in the first 6 months of life. Infants of women immunized in pregnancy were less likely to be small for gestational age, had a higher mean birth weight, and had lower hospitalization rates for ILI than those born to women who did not receive the immunization. [39, 40, 41]  The efficacy of influenza vaccine in pregnancy was corroborated by a trial in Mali that demonstrated a 64.5 % reduction in influenza A infection in the first 5 months of life among mothers vaccinated in the third trimester. [42]

Influenza poses a significant threat to maternal and infant health and much of the morbidity and mortality can be mitigated by routine influenza immunization in pregnancy.

Safety of Influenza Vaccine in Pregnancy

Several studies and systematic reviews have assessed the safety of both seasonal influenza vaccine and pandemic H1N1 influenza vaccine in pregnancy and revealed no safety concerns among women or their infants. The most commonly reported maternal adverse event is pain at the injection site. Adverse obstetric and neonatal outcomes, including rates of spontaneous abortion, preterm delivery, low birth weight and birth defects are similar or lower among women receiving influenza vaccine as compared with those who are not immunized. [43, 44, 45]  A review comparing safety outcomes between H1N1 influenza vaccine and seasonal vaccine reported similar incidences of preterm birth, very preterm births, low birth weight, very low birth weight, small for gestational age, spontaneous abortion, stillbirths and congenital anomalies. [46]

Though the safety profile of influenza vaccine administered in the first trimester is more limited, an observational study of 52,856 infants with maternal influenza vaccine exposure in the first trimester found no increased risk for major structural birth defects when compared with infants unexposed to maternal influenza immunization. [47]  A single study in 2017 reported an increased odds of having had pH1N1 influenza vaccination in the preceding 28 days among those women who had a spontaneous abortion (SAB) in the first trimester compared with those who did not, an association that was only true among women who had also been vaccinated in the previous influenza season with a pH1N1 vaccine. [48]  No association was found among women receiving pH1N1 vaccine in other trimesters nor among first time recipients of pH1N1 vaccine in the first trimester. There were several limitations of this study. Only small numbers of women (11% of either cohort) received the influenza vaccination, and spontaneous abortion is a difficult outcome to ascertain given high rates of first-trimester loss overall, and uncertain reporting rates of SAB and influenza vaccination could have been incompletely reported and recorded making it difficult to interpret the results. In addition, it is important to note that this study estimated the odds ratio of vaccination in women who had miscarriage compared to those who did not. The study did not estimate the risk of miscarriage after influenza vaccination, therefore, the findings cannot be used to estimate the probability of miscarriage for pregnant women who received H1N1 containing vaccine. Though few studies have determined the impact of immunization on SAB, existing literature is not consistent with these recent findings. Analysis of the Vaccines and Medications in Pregnancy Surveillance System (VAMPSS) identified a non-significant Hazard Ratio (HR) of 1.09 (95% CI 0.49–2.40) for SAB among vaccine-exposed vs. unexposed women from 2010 to 2014. [49, 50, 51]  The association between recurrent pandemic influenza immunization and SAB does not establish a causal relationship, and further studies are ongoing to clarify this association.

Given the significant burden of influenza disease on pregnant women and their infants and the reassuring safety data on vaccination in pregnancy, ACOG, the Society for Maternal and Fetal Medicine (SMFM), CDC and ACIP continue to recommend influenza immunization in each pregnancy to be administered in any trimester. [52, 53, 54]  Consistent with principles of maternal vaccination, only the inactivated influenza vaccine should be administered to avoid the theoretical risk of disease transmission from a live attenuated vaccine. [3]  ACOG strongly recommends that influenza immunization be provided as a component of routine prenatal care. Studies have shown that vaccine uptake rates are highest when obstetricians recommend, stock, and provide immunization at the site of prenatal care. [9, 12]

Live Attenuated Influenza Vaccine (LAIV)

Due to theoretical risks of live vaccines, LAIV is not recommended for use in pregnancy. [55]  As described above, all pregnant women should be immunized with the seasonal inactivated influenza vaccine. Due to lower than expected efficacy, the CDC does not recommend use of the nasal spray LAIV for any age group or population. [36]

Recommendations

• Influenza immunization is recommended for all pregnant women as part of routine prenatal care in each pregnancy during influenza season.

• Influenza immunization should be offered as early as possible during flu season and can be administered in any trimester.

• Live-attenuated influenza vaccine (LAIV) is not recommended for any age group or population.

Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap)

In October 2022, the FDA approved Tdap (Boostrix) for third trimester maternal vaccination to prevent pertussis infection in infants younger than 2 months. Since 2012, the CDC Advisory Committee on Immunization Practices has recommended pregnant women receive a dose of Tdap, regardless of the interval since their last tetanus or diphtheria toxoid-containing vaccine. [56]  

History and Rationale for Tdap vaccine in Pregnancy

Although tetanus and diphtheria have largely been eradicated in the United States, in part due to robust recommendations for Td immunization across the lifespan and post-exposure prophylaxis. Pertussis, a respiratory infection caused by Bordetella pertussis, has continued to be reported in high numbers among the general population. Morbidity and mortality from pertussis in the United States disproportionately affect infants 3 months of age and younger, more than half of whom are exposed to pertussis from an infected parent. [4, 9]  Current CDC recommendations call for infant immunization with DTaP vaccine starting at 2 months, with protection developing after 6 months of age. The inability to protect infants under 6 months results in a window of vulnerability, particularly for newborns, in whom pertussis infection has significant morbidity and mortality.

Initial approaches to neonatal protection attempted to reduce neonatal exposure to pertussis by recommending immunization of previously unvaccinated postpartum women and other close contacts of neonates with Tdap. ACIP recommended this “cocooning” approach starting in 2006, and continues to recommend that previously unimmunized adolescent and adult caregivers receive Tdap at least two weeks prior to infant contact. [57]  However, cocooning alone inadequately protected infants, and infant deaths secondary to pertussis continued to increase. As studies confirmed that antibodies induced by maternal vaccination efficiently transferred across the placenta providing effective passive immunity in infants ineligible for active immunization, ACIP adopted a strategy of administering Tdap in the third trimester to pregnant women who had not been previously vaccinated. [4]  Record high number of cases of pertussis in 2012, low uptake of the recommended Tdap vaccination in pregnancy, new data suggesting that maternal anti-pertussis antibodies are short-lived after vaccination, and a growing body of evidence on safety of pertussis vaccination in pregnancy led to the current recommendation for Tdap administration in each pregnancy, regardless of prior immunization history. [56]

Several studies have demonstrated the effectiveness of maternal vaccination as a strategy to prevent infant pertussis. In the UK, a retrospective study found maternal vaccination in the third trimester to be 90% effective for infants under 2 months [58] , results that were consistent with a case-control study in England and Wales that demonstrated 93% effectiveness [59]  and a retrospective cohort in California demonstrating 91% effectiveness. [60]

The ideal timing of Tdap administration continues to be investigated. Studies on maternal antibody transfer suggest that that immunization should ideally take place after 27 weeks gestation, when placental antibody transfer increases, yet early enough to allow sufficient time for maternal immune response to develop prior to delivery. [61]  While current recommendations suggest administration any time from 27 to 36 weeks, ACIP encourages administration as early as possible in that window to maximize passive antibody transfer to the fetus. [9, 56]

Safety of Tdap vaccine in Pregnancy

In 2010, a review of the U.S. based Vaccine Adverse Event Reporting System (VAERS) database did not reveal any concerning outcomes for mothers or infants following maternal Tdap immunization. [62]   Several large retrospective studies in the US and UK have demonstrated similar or lower rates of stillbirth, neonatal death, hypertensive diseases of pregnancy and low birth weight. [63, 64]  A recent systematic review assessing safety of Tdap immunization in pregnancy included 21 studies on women who had received either Tdap or Tdap-IPV and concluded that Tdap administration in pregnancy was not associated with clinically significant harms for women, their fetus, or neonate. [65]

Recommendations

The following recommendations regarding Tdap immunization in pregnancy are provided by ACIP [56]  and endorsed by ACOG [9] :

• Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) immunization is recommended once during each pregnancy, including in women with prior vaccination. Optimal vaccine timing is between 27 and 36 weeks with ideal administration as early as possible in that window to maximize passive neonatal immunity. Tdap may also be given at any time in pregnancy.

• For women with incomplete or unknown tetanus vaccination status, the tetanus and reduced diphtheria toxoid (Td) series should be initiated in pregnancy to protect against maternal and neonatal tetanus.  The recommended timeline is 0 weeks, 4 weeks and 6-12 months. One of these doses should be replaced with Tdap, ideally between 27 and 36 weeks gestation.

• For pregnant women with special circumstances in which Td or Tdap vaccine would be indicated (wound management, pertussis outbreak), immediate vaccination should be provided according to guidelines. If Td booster is indicated at any time in pregnancy, pregnant women should be given Tdap.

• Revaccination in the third trimester is not indicated for women vaccinated during that pregnancy for another indication.

Hepatitis A

Hepatitis A virus (HAV), an RNA picornavirus, causes fever, nausea, abdominal pain and jaundice secondary to an acute liver infection.  HAV is primarily transmitted through person-to-person contact through the fecal-oral route and does not lead to chronic liver infection. [66]  The CDC recommends HAV immunization for adults at increased risk for HAV infection. Risk factors for acquiring HAV include medical comorbidities (chronic liver disease including those who are infected with hepatitis B or hepatitis C, and individuals receiving clotting-factor concentrates due to clotting-factor deficiencies) and increased exposure risk (travel to endemic areas, exposure to individuals with HAV, men who have sex with men, IV drug use, persons exposed to biological specimens). Post-exposure prophylaxis is also available and both immune globulin and hepatitis A vaccine are recommended post-exposure for previously unimmunized individuals. [67]  The safety of HAV immunization in pregnancy has not been determined; however, hepatitis A vaccine is an inactivated vaccine with extremely low potential for maternal or fetal harm. 

Recommendation

• Pregnancy is not a contraindication to vaccine administration and ACIP and ACOG advise HAV vaccine in pregnancy for women in whom the risk of HAV infection exceeds the theoretical risk of immunization, which may be the case for pregnant women who plan to travel to areas where there is an increased risk for exposure to hepatitis A. [67, 68]

• Pregnant women who have been exposed to individuals with HAV infection and have not previously been immunized should receive post-exposure prophylaxis as described above. Immune globulin does not pose a risk in pregnancy and exposed pregnant women should receive both immune globulin and HAV immunization as soon as possible after exposure. [68]

Hepatitis B

Hepatitis B (HBV) is a DNA virus transmitted through infected blood and bodily fluids and can result in both acute and chronic liver infection. Chronic disease states can lead to long-term sequelae including cirrhosis, hepatocellular cancer, liver failure, and death. Risk factors for HBV infection include persons with more than one sexual partner in the past 6 months or with a recent diagnosis of an STI, history of an HBV positive partner or household contact, or history of IV drug use. [69]   HBV infection in pregnancy, both acute and chronic infection, poses a risk of vertical transmission with perinatally-acquired infection conferring the greatest risk of long-term consequences.

HBV vaccine is an inactivated recombinant DNA vaccine and is highly effective at preventing HBV infection. Pregnancy is not a contraindication to hepatitis B vaccine and both ACIP and ACOG recommend HBV immunization for pregnant women at risk of infection. [68]  Though safety data on HBV vaccine in pregnancy is limited, no fetal anomalies or developmental concerns and similar rates of preterm labor and stillbirth in vaccinated and unvaccinated groups. [70]  Routine prenatal screening for HBsAg is recommended to detect HBV carriers and to ensure neonatal immunoprophylaxis at birth. The combination of hepatitis B immunoglobulin (HBIG) and hepatitis B vaccine administered to neonates of mothers with chronic HBV infection within 12 hours of birth decreases rates of perinatal HBV infection by 85-95%. [68]

Recommendations:

• ACIP and ACOG recommend HBV immunization for pregnant women at risk of infection. 

• Pregnancy is not a contraindication to hepatitis B vaccine.

• Routine prenatal screening for HBsAg is recommended to detect HBV carriers and to ensure neonatal immunoprophylaxis at birth if needed.

Haemophilus influenzae type B (Hib)

Haemophilus influenzae type B (Hib) is an encapsulated gram-negative coccobacillus that was previously the most common cause of bacterial meningitis in children under 5 years old. After routine childhood immunization was introduced in 1988 more than 95% of the disease burden has been eliminated. Hib immunization continues to be recommended routinely in children under 5 years and is also recommended for adults at increased risk for invasive Hib disease due to chronic conditions including sickle cell disease, leukemia, HIV or functional asplenia. [71]

Hib vaccine is an inactive conjugate vaccine and therefore presents a low risk for maternal or fetal harm. Due to the primarily childhood burden of disease from Hib infection, maternal immunization has been studied as a strategy to protect young infants before active immunization is available. Initial small studies on Hib administration in the third trimester demonstrated safety for both pregnant women and their infants. [7]

Recommendations

• Due to both limited data and limited use of this vaccine in pregnancy, there is currently no recommendation from the CDC or ACIP on the use of Hib immunization in pregnancy. [18]

Meningococcal Disease

The encapsulated Neisseriameningitis gram-negative bacterium causes significant morbidity and mortality through meningococcal meningitis and bacteremia. Meningococcal conjugate vaccines (MCV4 and MenACWY) are effective against meningococcal disease. MCV4 immunization is routinely recommended for children aged 11-18 years and for adults with conditions that increase risk of infection (living in dormitories or military barracks, individuals with complement component deficiencies, functional or anatomic asplenia, HIV infection or those exposed to disease in an outbreak.

All meningococcal vaccines are inactivated and therefore low risk for adverse outcomes in pregnant women or their offspring. While available data confirms safety of meningococcal immunization in pregnancy, most studies involved MPSV4 rather than MCV4. Of note, the meningococcal polysaccharide vaccine (MPSV4) was previously available in the United States; however, it was discontinued in 2017 following evidence of waning immunity. [72]   A systematic review in 2012, found no safety concerns following maternal immunization with MPSV4 with no differences in preterm birth, neonatal mortality, low birth weight or fetal anomalies. [70]  One large randomized control trial in Mali, compared outcomes for women immunized in the third trimester with MCV4 or inactivated influenza vaccine and found no safety concerns with either vaccine and similar rates of preterm birth, similar birth weight and other obstetrical complications. The most common adverse event reported was pain at the injection site which was higher among women receiving MCV4. [42]

Recommendations

• ACIP recommends that pregnant women at increased risk for meningococcal disease be immunized according to existing adult recommendations. [55]

• Though no risks of immunization have been identified, the potential risk of disease exposure should be balanced against the theoretical risk of vaccine administration. [3]

Pneumococcal polysaccharide (PPSV23)

Streptococcus pneumoniae is a gram-positive bacterium that results in pneumonia, bacteremia, meningitis and otitis media. Childhood immunization against pneumococcal disease, initially with PCV7 and later with PCV13 has been routine since 2000 and has led to significant decreases in morbidity and mortality in children and adults. [73]  An expanded PPSV23 as well as PCV13 is recommended for children and adults with increased risk of invasive pneumococcal disease. At risk groups include those with chronic medical conditions, individuals with functional or anatomic asplenia, immunocompromised persons (including those with HIV), and individuals with cerebrospinal leaks or cochlear implants and all adults 65 years or older. Chronic medical conditions include chronic heart disease, chronic lung disease including asthma, pre-existing diabetes, cigarette smoking, alcoholism, and chronic liver disease. [74]

Routine immunization in pregnancy is not recommended by the CDC, as there is insufficient data on the safety of pneumococcal immunization in the first trimester. Pneumococcal immunization in the second or third trimester does appear to be safe: a systematic review of observational studies demonstrated similar rates of spontaneous abortion, fetal anomalies and preterm labor as the general population. [70]  A randomized control trial of PPSV23 administration in the third trimester identified no adverse outcomes, further demonstrating vaccine safety. [75]  While some have suggested maternal immunization against pneumococcal disease as a strategy to reduce infant pneumococcal infection, a Cochrane review in 2012 found no reduction in neonatal infection following third-trimester immunization. [76]  Despite limited safety data, pneumococcal immunizations contain no live particles and present an overall low risk to pregnant women and their fetuses. 

Recommendations:

• Pregnancy is not a contraindication to immunization

• ACIP recommends that pregnant women with medical risk factors for invasive pneumococcal disease be immunized with PPSV23 in pregnancy. [74]

• The safety of pneumococcal immunization in the first trimester has not been established, though no adverse events have been reported. [55]

• No guideline has been published regarding the use of PCV13 in pregnancy.  

Anthrax

Anthrax disease poses an overall low risk to the general population and routine pre-exposure immunization is only recommended for individuals at highest risk of exposure including military populations, environmental investigators, postal processing staff and individuals with laboratory exposures. [77, 78]

Sufficient data on the safety of anthrax vaccination in pregnancy is lacking, however, a recent retrospective study of inadvertent anthrax vaccination in pregnancy in a U.S. military population demonstrated no increased risk of birth defects among pregnant women immunized with the inactive AVA vaccine. [79]  An analysis of women in the Smallpox Vaccine in Pregnancy Registry who received the AVA vaccine within 28 days of or during pregnancy similarly found no increase in adverse outcomes as compared with non-AVA exposed pregnancies. [80]  Of note, a prior report on U.S. military women immunized in the first trimester did report an increased risk of birth defects as compared with never immunized women or women immunized after pregnancy (OR 1.20 CI 95% 1.02-1.42). [81]  A review of the findings revealed that this increase was attributable to a documented increase in atrial septal defects (ASD), a study code which was also used for patent foramen ovale, a common finding in preterm infants. As a result, ACIP concluded that while no safety concern had been identified for AVA administration in pregnancy, pregnant women should defer pre-exposure immunization until after pregnancy unless an imminent threat was present. [78]

Given the high morbidity and mortality of anthrax disease, pregnant women with an exposure to anthrax should receive AVA vaccination and anti-microbial treatment in concordance with published recommendations for adults. [78, 82]

Recommendations:

• Post-exposure AVA immunization, where the benefit greatly outweighs the theoretical risk of immunization, is recommended for all individuals exposed to anthrax including pregnant women. [78]  

• Given the low-risk of anthrax exposure, pre-event immunization is not recommended for pregnant women, as the benefit of immunization does not outweigh the theoretical risk of immunization. 

Japanese Encephalitis

Japanese encephalitis (JE) virus, a mosquito-borne RNA flavivirus, is the leading cause of vaccine-preventable encephalitis in Asia and the western Pacific. JE infection is usually asymptomatic or causes mild symptoms, however, less than one percent of infected individuals develop severe illness which is characterized by encephalitis and carries an approximately 25% mortality rate. [83, 84]  JE infection in pregnancy can lead to adverse outcomes including increased rates of spontaneous abortion and transplacental transmission resulting in intrauterine infection. [85]

JE immunization is currently recommended for travelers who plan to spend one month or more in endemic regions with active transmission or ongoing outbreaks. It is not recommended for short-term travelers unless they are traveling to high-risk regions, including rural or agricultural areas, where significant outdoor activities are planned or areas with ongoing outbreaks. [85]

No controlled studies in humans on the safety or immunogenicity of JE immunization in pregnancy have been published, though animal studies have demonstrated no evidence of harm to pregnant rats or mares and their offspring. [85, 86]  Due to the lack of safety data, JE immunization should generally be avoided in pregnant women. However, the CDC recommends that pregnant women traveling to endemic areas for extended periods should be considered for immunization with the inactivated JE vaccine if the theoretical risk of immunization is outweighed by the risk of JE virus infection. [55]

Recommendations:

• ACIP has no recommendation regarding JE immunization in pregnancy. Due to the lack of safety data, JE immunization should generally be avoided in pregnant women. [85]

• Pregnant women traveling to endemic areas for extended periods should be considered for immunization with an inactivated vaccine if the theoretical risk of immunization is outweighed by the risk of JE virus infection. [55]

Polio

Poliovirus, which can cause poliomyelitis, a crippling and deadly infection, was eradicated from the U.S. in 1979 but continues to circulate in several countries including Afghanistan, Pakistan, and Nigeria. Routine immunization against poliovirus with the inactivated polio vaccine (IPV) is recommended for all children and a single-lifetime booster dose is recommended for adult at increased risk for exposure who have previously completed the IPV series in childhood. [87]  Adults at increased risk include: travelers to areas or countries where polio is epidemic or endemic, individuals working with poliovirus in a laboratory setting, and healthcare workers in close contact with patients who may have poliovirus. [87]

No adverse effects of IPV immunization for pregnant women or their fetuses have been observed. [55]  Immunization with oral polio vaccine (OPV), a live attenuated vaccine, continues to be used in many parts of the world, though it was discontinued in the US in 2000. Several mass immunization programs in Finland and Israel that reached >90% of the population and included pregnant women revealed no safety concerns for pregnant women or their fetuses following immunization with OPV. [88, 89, 90]

Recommendations:

• Pregnancy is a precaution to immunization with inactivated polio vaccine (IPV).

• IPV may be administered to pregnant women. ACIP recommends that inactivated polio vaccine (IPV) be considered for pregnant women at risk for exposure to wild-type poliovirus. [91]

Rabies

Rhabdovirus infection affects the central nervous system, leading to neurologic symptoms and death if left untreated. Infection results from contact with the saliva of a human or animal infected with rhabdovirus and is usually transmitted from a bite injury. [92, 93]  Pre-exposure immunization with the inactivated rabies vaccine series is recommended for individuals at high risk for exposure including veterinarians, animal handlers, and travelers to endemic areas. Post-exposure immunization is indicated for both unvaccinated and previously vaccinated individuals, though unvaccinated persons should additionally receive rabies immunoglobulin. [93]

The CDC advises that due to the severe consequences of inadequately treated rabies, pregnancy is not a contraindication to post-exposure prophylaxis and pregnant women should be immunized and treated with human rabies Ig according to adult guidelines. [93]  Limited small observational studies have found no association between maternal rabies immunization and spontaneous abortion, preterm birth or teratogenesis. [94, 95, 96, 97]

Recommendations:

• Pregnancy is not a contraindication to rabies immunization.

• Pregnant women should follow the adult immunization guidelines for rabies.

• Post-exposure immunization is recommended for all pregnant women. 

• Pregnant women at high risk for rabies exposure should be considered for pre-exposure immunization. 

Typhoid

Typhoid is a life-threatening infection caused by the bacterium Salmonella Typhi. It is transmitted from personal contact with infected persons, food or water via the fecal-oral route and is most commonly encountered during travel to the developing world. [98]  Two typhoid vaccines are available in the US; a live attenuated vaccine and an inactivated vaccine. Routine typhoid immunization is not recommended in the US but may be recommended prior to travel to areas where typhoid is common. [99]

Recommendations:

• The CDC does not make any specific recommendations for typhoid immunization in pregnancy and no data is available on the safety of the inactivated typhoid vaccine in pregnancy. [55]

• In general, pregnant women are advised to avoid travel to areas with high rates of endemic typhoid.

• Immunization with the inactivated vaccine may be considered if the risk of acquiring the disease significantly outweighs theoretical risks of immunization.

• The live attenuated typhoid vaccine (Ty21a) should not be administered in pregnancy due to theoretical risks posed by live vaccines.

Yellow Fever

Yellow fever virus is a mosquito-borne RNA flavivirus that usually results in asymptomatic infection. Though rare, severe disease is associated with a high mortality rate resulting from multisystem organ failure and hemorrhage. Yellow fever is endemic in sub-Saharan Africa and in South America and proof of immunization against yellow fever is a requirement for travel to many countries in those regions. [100]

Yellow fever vaccine is a live-attenuated vaccine and therefore confers a small risk of reversion to a virulent state. Certain live vaccines have also been demonstrated to cross the placenta. Three well-characterized serious adverse events have been reported after yellow fever immunization: hypersensitivity or anaphylaxis, yellow fever vaccine-associated neurologic disease (YEL-AND) and yellow fever associated viscerotropic disease (YEL-AVD) which is characterized by multiorgan failure. [101]  A systematic review of adverse events in vulnerable populations identified eight studies concerning maternal yellow fever immunization seven of which identified no serious adverse events and rates of teratogenesis similar to the general population. [102]  One small study identified an increased risk of spontaneous abortion among women immunized with yellow fever in early pregnancy. This finding was not significant [103] , and a subsequent larger study did not demonstrate a greater risk for miscarriage after yellow fever immunization. [104]  A review of yellow fever safety in pregnancy concluded that the risks of adverse outcomes in pregnancy are similar to that of the general population. [89]

Yellow fever is the only live vaccine that is not contraindicated for pregnant women. ACIP considers pregnancy a precaution for yellow fever vaccination and advises immunization only for pregnant women at high risk for yellow fever exposure. This assessment should be based on location, seasonality and travel activities where the risks of exposure outweigh the risks of vaccination. If low-risk travel is unavoidable, pregnant women should be provided with a medical-waiver to meet travel requirements. Due to the potential risks of immunization with a live vaccine, non-pregnant women immunized against yellow fever should wait 4 weeks before attempting conception. [101]

Breastfeeding is also a precaution for yellow fever immunization as two cases, one probable and one confirmed, of YEL-AND have been described in breastfeeding infants whose mothers received yellow fever vaccine. As with pregnant women, nursing mothers should avoid yellow fever vaccine unless the potential risk of yellow fever exposure to the nursing mother exceeds the potential harm of immunization. [101]

Recommendations:

• Pregnancy is a precaution for yellow fever vaccination. [101]

• Pregnant women at high-risk for acquiring yellow fever should receive yellow-fever vaccine as the theoretical risk of immunization is outweighed by the risk for yellow fever infection. [91, 101]

• Pregnant and nursing women traveling to low-risk areas with a requirement for yellow fever immunization should be provided with a medical waiver to meet travel requirements. [101]

• Breastfeeding is a precaution for yellow fever vaccination and should be avoided in nursing mothers unless travel cannot be postponed or avoided and the risk for yellow-fever acquisition is high. [91, 101]

• Non-pregnant women immunized against yellow fever should wait 4 weeks before attempting conception. [101]

Measles, Mumps, Rubella

Measles and mumps are paramyxoviruses that are transmitted through direct person-to-person contact. While infection is usually mild, both infections can lead to long-term sequelae in a subset of infected individuals. Measles infection during pregnancy has been associated with an increased risk of spontaneous abortion, preterm birth, and low birth weight. Though measles was declared eliminated from the U.S. in 2000, outbreaks from imported cases have continued, often arising in unvaccinated communities. [105]  Mumps most commonly presents with parotitis and respiratory symptoms, and in rare cases can lead to orchitis, deafness or meningitis. Routine immunization against mumps has been available since 1967 and has reduced disease incidence by over 99%. [106]  Rubella, a Togavirus, can result in significant adverse outcomes if contracted in early pregnancy, including high rates of spontaneous abortion, neonatal death and congenital rubella syndrome (CRS). [107]

The CDC recommends routine childhood immunization with MMR, a live attenuated combination vaccine against measles, mumps, and rubella. They further recommend that certain at-risk groups including college and graduate students, international travelers, healthcare professionals, people who care for immunocompromised people and non-pregnant women of reproductive age, remain up to date with their MMR vaccination. [107]

Due to theoretical risks of live attenuated vaccines, MMR immunization is contraindicated in pregnancy; however, no safety concerns have been identified after inadvertent rubella or MMR immunization in pregnancy. Studies in Europe, Canada, Iran and Latin America have evaluated the outcomes of a combined total of over 3500 rubella-susceptible women who received rubella immunization (alone or in combination vaccines) in early pregnancy. Several of these studies found evidence of transplacental transmission of the rubella and mumps vaccine viruses, however, no cases of CRS were reported. [89]  Two studies reported no increase in low birth weight or prematurity after rubella immunization. [89]

In the US, where rubella has been eliminated since 2004, the theoretical risk of MMR vaccination in pregnancy outweighs the potential benefits, however, women who are inadvertently immunized in pregnancy should be reassured, and MMR immunization in pregnancy should not be considered an indication for pregnancy termination.

To avoid the risks of rubella infection in pregnancy, reproductive-aged women should be immunized with MMR prior to conception. The CDC and ACOG recommend that pregnant women be screened for rubella immunity during routine prenatal care so that non-immune women can be identified in order to receive MMR immunization immediately postpartum, prior to discharge from the hospital. [107]  This strategy of postpartum immunization provides protection for subsequent pregnancies while reducing potential exposures for infants. MMR vaccination is safe in the postpartum period: there are no reports of transmission of measles or mumps from vaccine recipients to household contacts and no confirmed cases of transmission of rubella virus from immunization have been reported.

Recommendations: 

• Pregnancy is a contraindication for MMR immunization. Women should be asked about their pregnancy status prior to immunization. Routine pregnancy testing is not recommended prior to vaccine administration. [91, 107]

• Women should be advised to wait 4 weeks after immunization before becoming pregnant, due to the theoretical risk of immunization with a live vaccine. [91, 107]

• Pregnant women should be screened for rubella immunity in pregnancy. Rubella non-immune women should be offered MMR immunization postpartum, prior to hospital discharge. [91, 107]

• No cases of congenital rubella syndrome have been reported after inadvertent MMR immunization in pregnancy. MMR immunization in pregnancy should not be considered an indication for pregnancy termination. 

Varicella

Varicella-zoster virus (VZV) is a herpes virus that causes chickenpox and shingles. It is highly contagious and transmitted by direct contact with skin lesions of an infected person or through inhalation of aerosolized particles. [108]  In 1995, a live attenuated varicella vaccine was introduced in the US and included in routine childhood immunization schedules. As a result, the incidence of varicella decreased by 90% over the next ten years. [4, 109]

Pregnant women are more likely to have complications from varicella infection and experience higher morbidity and mortality compared with the general population, primarily due to VZV pneumonia. [110]  Maternal varicella infection in the first or second trimester can lead to a rare but severe congenital varicella syndrome (CVS), which manifests as skin scarring, limb hypoplasia, low birth weight, microcephaly, cortical atrophy, chorioretinitis, cataracts, and other anomalies. [111]  The risk of CVS after maternal chickenpox varies by gestational age, with rates of infection documented at 0.6% before 12 weeks, 1.4% between 13 and 28 weeks and zero risk beyond the second trimester. [111, 112, 113]  Maternal varicella infection near the time of delivery poses a risk for neonatal varicella disease.

The CDC recommends routine screening of pregnant women for evidence of varicella immunity. Prior history of infection is 97-99% predictive of seropositivity. As such, immunity can be determined through a self-reported history of chickenpox or prior vaccination.  If a patient is unsure of her immune status, serologic testing is recommended in early pregnancy. Ideally, non-immune women should be identified and vaccinated prior to pregnancy. Pregnant women who are identified as varicella non-immune should be immunized immediately postpartum and prior to discharge from the healthcare facility. A second dose should be administered at the postpartum visit, 4 weeks after the initial dose. Due to theoretical risks of live vaccines, women should be counseled to avoid pregnancy for 4 weeks following immunization. Pregnancy is a contraindication to varicella immunization due to a theoretical risk of maternal immunization resulting in congenital varicella syndrome. [111]

The Merck/CDC Pregnancy Registry for VZV-Containing Vaccines was established in 1995 and followed reports of women inadvertently immunized with a varicella vaccine within 3 months of pregnancy or during pregnancy until March 2012. In over 10 years, no cases of CVS were reported, and fetal anomalies were reported at rates similar to the general population.  Due to the rare incidence of CVS after wild-type varicella infection, this database cannot exclude the possibility of CVS after varicella immunization, and women inadvertently immunized in pregnancy or in the month prior to conception should be counseled on theoretical risks posed by live attenuated vaccines. [114]  Varicella vaccination in pregnancy should not be considered an indication for pregnancy termination. [55]

Pregnant women who are non-immune and exposed to varicella in pregnancy should receive postexposure prophylaxis with VZV immunoglobulin (VariZIG). VariZIG is recommended by the CDC for high-risk groups, including non-immune pregnant women, and should be administered as soon as possible after exposure, and ideally within 96 hours of exposure to reduce risk of disease in the pregnant woman and thereby also reduce the risk to her fetus. VZV vaccine is not recommended after exposure in pregnancy as it is contraindicated in pregnancy. [115]

Recommendations:

• Pregnancy is a contraindication to varicella immunization.

• Ideally, non-immune women should be immunized prior to pregnancy. Women should be counseled to avoid pregnancy in the 4 weeks following varicella immunization.

• Pregnant women should be screened for evidence of varicella immunity as determined by self-report of chickenpox or prior vaccination. If a patient is unsure of her immune status, serological testing is recommended early in pregnancy.

• Varicella non-immune pregnant women should be immunized immediately postpartum, prior to hospital discharge. A second dose should be administered 4 weeks after the first dose, at the postpartum visit.

• No cases of congenital varicella syndrome have been reported after varicella immunization. Varicella vaccination in pregnancy should not be considered an indication for pregnancy termination. [55]  

• Pregnant women who are non-immune and exposed to varicella in pregnancy should receive post-exposure prophylaxis with VZ immunoglobulin (VariZIG) as soon as possible after exposure. [115]

Human Papillomavirus

High-risk human papillomaviruses are sexually transmitted viruses that can cause genital warts and cervical, vaginal and vulvar cancers. HPV vaccination with the 9-valent HPV vaccine is routinely recommended for adolescents aged 11 years or 12 years, and for adults through age 45 years who were inadequately vaccinated previously. [116, 117]  Immunization for HPV may be initiated in children as young as 9 years old. The 2-valent and 4-valent HPV vaccines are no longer available in the United States.

Early data on inadvertent HPV vaccination in pregnancy are reassuring and there is no recommendation for pregnancy testing prior to HPV vaccine administration. No differences in pregnancy complications or major birth defects were noted after administration of the 4-valent HPV vaccine. [118]  A study on spontaneous abortion after HPV immunization in the UK found no increased risk after a single dose, though did report a higher risk among women receiving their second dose in pregnancy. [119]

Recommendations:

• HPV vaccines are not recommended in pregnant women as it provides no immediate benefit to the pregnant woman or her fetus.

• Pregnancy testing is not needed before vaccination. [120]

• Women that have started the HPV series and are found to be pregnant should defer the remaining doses until postpartum. [55]

• Women who are immunized inadvertently in pregnancy should be reassured and HPV immunization is not an indication for pregnancy termination. [55]

Vaccinia (Smallpox)

Smallpox is a highly infectious disease with significant morbidity and mortality that is caused by the Variola virus. Due to a widespread vaccination program, the virus has been eradicated globally since 1977, and routine vaccination programs for the general population ended in the US in the 1970s. A smallpox vaccine is still recommended as pre-exposure prophylaxis for specific populations who work with orthopoxviruses, such as monkeypox, cowpox, and others. This live vaccine contains the vaccinia virus which induces cross-protective immunity against other orthopoxviruses. [121]

Several serious adverse events have been reported following vaccinia immunization, including progressive vaccinia, postvaccinial encephalitis, eczema vaccinatum and myopericarditis. When administered in pregnancy, smallpox vaccine has been known to cause fetal infection with fetal vaccinia. [18]  Data from a recent, large-scale US smallpox immunization program of military and select civilian personnel identified no cases of progressive vaccinia or eczema vaccinatum among immunized individuals. [122]  An increased risk for myopericarditis following immunization was identified. [123]

Smallpox vaccination in a pre-event setting is not recommended during pregnancy or for women attempting pregnancy due to risks of fetal vaccinia, a rare but often fatal complication. [55, 91]  A review of 376 women inadvertently immunized with smallpox vaccine during pregnancy or within 28 days of pregnancy identified no cases of fetal vaccinia and no increased risks of spontaneous abortion, stillbirth or preterm birth. [124]  Giving these overall reassuring findings, the CDC advises that smallpox vaccination during pregnancy should not ordinarily be an indication for pregnancy termination. [55]

Pregnant women with a definite exposure to smallpox (through face-to-face contact, household contact or close-proximity contact with a smallpox patient) should be vaccinated. In these circumstances, the potential maternal and fetal harms of smallpox infection outweigh the overall low risks of immunization. [55]

Recommendations:  

• Smallpox vaccination in a pre-event setting is not recommended during pregnancy or for women attempting pregnancy due to risks of fetal vaccinia, a rare but often fatal complication. [55, 91]

• Women inadvertently immunized with smallpox vaccine should be counseled on the possible concerns for the fetus. Smallpox vaccination during pregnancy should not ordinarily be an indication for pregnancy termination. [55]

• Pregnant women with a definite exposure to smallpox (through face-to-face contact, household contact or close-proximity contact with a smallpox patient) should be vaccinated. [55]

Breastfeeding and Vaccines

The two vaccines that are generally not recommended for breastfeeding mothers are smallpox vaccine and yellow fever vaccine. Smallpox immunization presents the risk of person to person transmission through direct contact, and is therefore contraindicated for breastfeeding mothers due to the theoretical concern for direct horizontal transmission to the infant. [91]  Breastfeeding is a precaution for yellow fever vaccination due to two reports of yellow fever vaccine-associated neurologic disease (YEL-AND) in breastfed infants. If the risks of yellow fever exposure exceed the overall low risk of immunization, the nursing woman should be vaccinated.

All other vaccines, both inactivated and live-attenuated, can be administered safely to lactating women without interruption in infant feeding patterns. Inactivated vaccines pose no risk to the infant as they cannot cause infection in either the lactating woman or her child. Live vaccines are capable of replication; however, mumps, measles, and varicella virus have not been identified in breast milk. Although rubella vaccine virus has been found in breastmilk, the virus has not been found to infect the infant and breastfeeding is not a contraindication to postpartum immunization. The CDC advises that recombinant, subunit, polysaccharide and conjugate vaccines pose no risk to breastfeeding mothers or their infants.

Recommendations  [91] :

• Inactivated, recombinant, subunit, polysaccharide, conjugate and toxoid vaccines pose no risk to breastfeeding women or their infants.

• Other than smallpox and yellow-fever, all other live-attenuated vaccines are safe to administer to breastfeeding women.

• Breastfeeding is a precaution for yellow fever vaccine and should be avoided unless the risk for yellow fever acquisition is high. 

Immunization Strategies

Despite strong national recommendations for influenza and Tdap immunization in pregnancy, overall maternal immunization rates remain far below the Healthy People 2020 goal of 80% coverage. Since the 2009 H1N1 pandemic, influenza vaccine administration in pregnancy has increased to 50%. Published rates for Tdap vaccine uptake in pregnancy vary, data from the Vaccine Safety Datalink found that only 42% of women having a live birth received the vaccine during pregnancy and national rates likely hover near 50%. [125, 126, 127, 128]

A recent review describes multifactorial reasons for the low uptake of maternal immunization including concern for the safety of vaccines in pregnancy, belief that the vaccine is not necessary, lack of knowledge about the vaccine or disease, lack of recommendation from a healthcare worker, and barriers to access or availability. [129, 130]  Immunization rates are significantly higher when a health care provider recommends and administers immunizations on site as compared to either no recommendation or a recommendation without immediate availability for vaccine administration.9 The recommendation from national organizations includes prenatal care providers strongly recommending, stocking, and administering vaccines in their offices. Strategies for increasing vaccine uptake include incorporating immunizations into standard prenatal care and establishing automatic prompts for vaccine administration through electronic medical record alerts and order sets. [1, 131]

Summary

Summary Recommendations: 

• Women of reproductive age should be screened for their immunization status and any indicated immunizations should be administered according to published adult immunization schedules.

• In general, inactivated immunizations present a low risk for adverse outcomes in pregnant women and their offspring.

• With the exception of yellow fever and smallpox, live vaccines are relatively contraindicated in pregnancy. All live vaccines should be avoided during pregnancy unless the risk of disease exposure exceeds the potential risk of immunization.

• Maternal immunization has been demonstrated to be a safe and effective strategy for protecting both pregnant women and their infants from severe vaccine-preventable disease, including influenza and pertussis.

• Influenza vaccine is recommended in each pregnancy and can be administered in any trimester.

• Tdap is recommended in every pregnancy, between 27 and 36 weeks of gestation.

• Other vaccines may be indicated in special circumstances, due to medical comorbidities, travel, or workplace exposures.

• Smallpox and yellow-fever vaccine should be avoided in pregnant women unless the risk of disease exceeds the risk of immunization. All other vaccines are safe to administer to breastfeeding women.

• To increase uptake of vaccines, prenatal care providers should strongly recommend, stock, and administer vaccines in their offices.

Recommendations for Vaccines in Pregnancy. (Open Table in a new window)

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Author

Mae Bridget Spelke, MD Resident Physician, Department of Obstetrics and Gynecology, Women and Infants Hospital of Rhode Island, The Warren Alpert Medical School of Brown University

Disclosure: Nothing to disclose.

Coauthor(s)

Erica J Hardy, MD, MA, MMSc Assistant Professor of Medicine (Clinical), The Warren Alpert Medical School of Brown University; Attending Physician, Obstetric and Consultative Medicine and Infectious Diseases, Director, Women’s Infectious Disease Consultation Service, Division of Obstetric and Consultative Medicine, Department of Medicine, Women and Infants Hospital of Rhode Island; Attending Physician, Division of Infectious Disease, The Miriam Hospital

Erica J Hardy, MD, MA, MMSc is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, Infectious Diseases Society of America, North American Society of Obstetric Medicine, Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

Maureen G Phipps, MD, MPH Chace-Joukowsky Professor and Chair, Department of Obstetrics and Gynecology, Professor, Department of Epidemiology, Assistant Dean for Teaching and Research in Women’s Health, The Warren Alpert Medical School of Brown University; Chief of Obstetrics and Gynecology, Director, Brown University/Women and Infants Hospital National Center of Excellence in Women’s Health, Women and Infants Hospital of Rhode Island; Chair and Executive Chief of Obstetrics and Gynecology, Care New England Health System

Maureen G Phipps, MD, MPH is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Gynecological and Obstetrical Society, American Public Health Association, Association of Professors of Gynecology and Obstetrics, Council of University Chairs of Obstetrics and Gynecology, North American Society for Pediatric and Adolescent Gynecology, Society for Academic Specialists in General Obstetrics and Gynecology, Society for Gynecologic Investigation, Society for Research on Adolescence, The Foundation for Exxcellence in Women's Health

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Which part of the female breast is functionally similar to sebaceous glands?

Which of the following is not true about progesterone?