In recent years, the public health and medical communities have faced several emerging infectious disease outbreaks, including SARS and monkeypox, and much consideration has been given to preparation for a future influenza pandemic. In addition, experience with bioterrorism attacks (anthrax) and emergency response preparedness (smallpox vaccination) has been gained. These events required careful consideration of recommendations for the care of pregnant women.
The SARS outbreak of 2003, caused by a newly identified coronavirus, affected >8,000 persons worldwide (22
). Reports suggest that the clinical course and outcomes of SARS might be more severe for pregnant than for nonpregnant women (23
). Identifying appropriate treatment modalities during the SARS outbreak was challenging, given the lack of information about the newly identified disease. Ribavirin was initially chosen because of its broad antiviral spectrum. Corticosteroids were used in an attempt to limit the tissue damage caused by the inflammatory response (24
). However, issues regarding the teratogenicity of these medications have been raised, further complicating decisions about their use during pregnancy. Some animal studies have suggested that ribavirin is teratogenic, but limited experience is available regarding its effects on human pregnancies (25
). Animal studies and some human studies have demonstrated an increased risk for birth defects when corticosteroids are used during pregnancy (26
). In spite of this information, all but 1 of the 12 pregnant women with SARS reported from Hong Kong Special Administrative Region, People's Republic of China Special Administrative Region, People's Republic of China received ribavirin and corticosteroid treatment (22
), probably because their illness was life-threatening. On the basis of more recent data, the efficacy of ribavirin and corticosteroids in the treatment of patients with SARS has been questioned (24
). Other medications, such as interferons, have been proposed for use in future SARS outbreaks, but use of these medications in pregnant women may also be of concern.
In June 2003, the first outbreak of monkeypox in the Western Hemisphere occurred in the United States (27
). Because of the high death rate associated with monkeypox on the African continent (28
) and lack of experience with monkeypox in the United States, CDC recommended smallpox (vaccinia) vaccination (≈85% effective against monkeypox) (29
). The outbreak was traced to importation of infected rodents that infected pet prairie dogs and other small mammals kept as pets. Smallpox vaccination during pregnancy poses a low risk for fetal vaccinia, which can lead to preterm birth, and fetal and neonatal death (30,31
). However, women who were exposed were advised to receive the smallpox vaccine regardless of their pregnancy status (32
), given the life-threatening risk associated with monkeypox infection.
Planning for a future influenza pandemic must include specific considerations for pregnant women (33
). Because pregnancy has been shown to increase the risk for influenza-associated complications (34
), pregnant women are considered a high-risk group and are recommended to receive influenza vaccination during interpandemic years (35
). This vaccine is inactivated and is considered safe for pregnant women. It is reformulated each year to include the anticipated viral strains of the upcoming influenza season.
Pregnant women also should be considered at increased risk from influenza infection in the event of pandemic influenza. Vaccination of pregnant women not only benefits the woman herself but also indirectly confers immunity to her infant, which can last the first 6 months of life when vaccination is not approved for children (36
). During a pandemic, an effective vaccine may initially be unavailable or in limited supply. In such a situation, chemoprophylaxis will be an important option for pregnant women. Unfortunately, no information is available regarding the effects on the fetus of neuraminidase inhibitors (oseltamivir and zanamvir), the medications likely to be useful in an H5N1 pandemic (36
). Thus, weighing the risks associated with infectious exposure in a pregnant woman and risks associated with medication exposure to her unborn child is difficult.
The anthrax attacks of 2001 prompted the first, large-scale recommendations for use of prophylactic medications in response to bioterrorism. The recommended medication for initial antimicrobial drug prophylaxis of asymptomatic exposed adults was ciprofloxacin, with doxycycline and amoxicillin as alternative therapies if the strain was susceptible (37
). Because of an observed association between fluoroquinolones and joint and cartilage toxicity in juvenile animals (38
), ciprofloxacin is generally not recommended during pregnancy if efficacious alternatives are available. Although information on the safety of ciprofloxacin in pregnant women was lacking, the available limited information suggested that its use during pregnancy was unlikely to be associated with a high risk for structural birth defects. In addition, maternal exposure to tetracyclines, which include doxycyline, carries the known risks of staining the primary teeth, concern about bone growth and abnormal tooth enamel in the fetus (39
), and rare instances of hepatic necrosis in pregnant women. Although penicillins are considered safe during pregnancy, the fact that Bacillus anthracis strains may have penicillinase activity led to the recommendation that amoxicillin be used for prophylaxis only if the specific strain was shown to be penicillin sensitive. On the basis of these considerations, CDC recommended that ciprofloxacin be the antimicrobial drug of choice for initial prophylactic therapy of asymptomatic pregnant women exposed to B. anthracis during the 2001 anthrax attacks (40
). The American College of Obstetricians and Gynecologists Committee on Obstetric Practice endorsed these recommendations and emphasized that prophylaxis be limited to women exposed to a confirmed environmental contamination or a high-risk source, as determined by local public health officials (41
In 2003, the United States embarked on an effort to vaccinate public health and medical bioterrorism response teams against smallpox. In the absence of circulating smallpox virus, vaccination in pregnant women or women who desire to become pregnant within 28 days of the vaccination is contraindicated because of the risk for fetal vaccinia (30
). However, after an intentional attack, pregnancy should not be considered an absolute contraindication to vaccination (30
). In the event of exposure or high risk for exposure to smallpox, pregnant women are advised to receive the vaccine because the risk for death and serious illness from smallpox (particularly during pregnancy) outweighs the risk for fetal vaccinia.
Despite the recommendations that pregnant women avoid vaccination, several pregnant women were inadvertently vaccinated during the smallpox vaccination campaign and were encouraged to enroll in the National Smallpox Vaccine in Pregnancy Registry (42
). Preliminary results from the registry suggest that the rates of pregnancy loss, preterm birth, and birth defects among infants born to vaccinated women did not increase, but evaluation is ongoing. Pregnancy registries such as this and the Department of Defense Birth and Infant Health Registry (43
) should be considered whenever emergency response activities invoke the use of medications or vaccines with unknown effects on pregnant women and fetuses.
These examples demonstrate some of the challenges faced by pregnant women and their healthcare providers when considering prophylaxis and treatment in response to emerging infections or bioterrorism attacks. In most instances, information on the effects of the medication or vaccine on the fetus is limited. Decisions regarding appropriate prophylaxis and treatment of pregnant women must take into account the risks associated with specific medications or vaccines versus the risk for illness and death from a possible infectious exposure.