Women with Smallpox Vaccine Exposure During Pregnancy Reported to the National Smallpox Vaccine in Pregnancy Registry --- United States, 2003

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In the absence of circulating smallpox, pregnant women should not be exposed to live vaccinia virus contained in the smallpox vaccine. The smallpox vaccine should not be administered to women who are pregnant or might become pregnant within 4 weeks after vaccination because of the risk for fetal vaccinia, a rare but serious infection of the fetus. In addition, persons who have close contact (e.g., household contact or sexual contact) with pregnant women are advised to forego vaccination (1,2). To prevent inadvertent exposure of pregnant women to vaccinia virus, screening for pregnancy is a component of pre-event smallpox vaccination programs. To monitor outcomes of pregnancy in women exposed to smallpox vaccines, CDC, in collaboration with the Department of Defense (DoD) and the Food and Drug Administration (FDA), has established the National Smallpox Vaccine in Pregnancy Registry. This report summarizes data from the registry about these exposures. CDC and the Advisory Committee on Immunization Practices (ACIP) recommendations to screen for pregnancy as a contraindication to smallpox vaccination (1) appear to be effective at preventing inadvertent exposures.

The registry includes women found to be pregnant when vaccinated, those who became pregnant within 28 days of vaccination, and those who, while pregnant, were in close contact with a person vaccinated within 28 days (3). Cases of women inadvertently exposed to smallpox vaccine during pregnancy are reported to the registry by state health departments, health-care providers, CDC's Clinician Information Line, DoD, FDA, and through the Vaccine Adverse Event Reporting System (VAERS). Women reported to the registry will be monitored frequently during each trimester and at the conclusion of the pregnancy to document pregnancy outcomes. Outcomes will be tabulated by trimester and reported.

During November 5, 2001--April 24, 2003, women of reproductive age (18--44 years) were vaccinated against smallpox in three populations: military personnel, U.S. civilian health-care and public health workers, and some clinical research study volunteers. Overall, 103 women have inadvertently received smallpox vaccine while pregnant or have conceived within 4 weeks of vaccination.

DoD Vaccination Program

During December 13, 2002--April 22, 2003, a total of 62,222 women of reproductive age were screened for smallpox vaccination, and 52,185 were vaccinated in the military program; 85 were inadvertently exposed to smallpox vaccine during pregnancy. Of the 75 women with known vaccination status, 66 were primary vaccinees. The median age was 22 years (range: 18--35 years). On the basis of the estimated date of conception, 62 women conceived before vaccination and 23 conceived during the 4 weeks after vaccination.

Civilian Heath-Care and Public Health Workers

During January 24--April 24, 2003, a total of 6,174 women of reproductive age were vaccinated through the civilian program. Six were inadvertently exposed to smallpox vaccine during pregnancy. Three of the women were primary vaccinees. The median age was 31 years (range: 26--38 years). On the basis of the estimated date of conception, two women conceived within 1 week before vaccination and four conceived during the 4 weeks after vaccination. Two of the women had miscarriages during early pregnancy. An additional two pregnant civilian women were in close contact with persons recently vaccinated against smallpox. Neither of these women have had known signs or symptoms of vaccinia exposure.

Clinical Studies

During November 2001--April 24, 2003, a total of 12 women from clinical studies who had inadvertent exposure to smallpox vaccines during pregnancy have been reported to the registry. The denominator for women of reproductive age for this population is not available. The median age was 28 years (range: 18--42 years). Each of the women had a negative pregnancy test on the day of vaccination.

Reported by: M Ryan, MD, JD Grabenstein, PhD, U.S. Dept of Defense. Smallpox Vaccine and Pregnancy Registry Team; K Broder, MD, EIS Officer, CDC.

Editorial Note:

Smallpox vaccine can cause fetal vaccinia, a rare but serious complication of exposure to the vaccine during pregnancy that often results in fetal or neonatal death and premature birth (4,5). Fetal vaccinia, which is postulated to occur following maternal viremia, is manifested by skin lesions and internal organ involvement (4,6). Approximately 50 cases of fetal vaccinia have ever been reported in the world and three have been reported in the United States. In 1924, an infant was born prematurely at 6 months' estimated gestational age (EGA) 4 weeks after the mother's vaccination during a smallpox epidemic; the infant had vaccinia-like skin lesions and died shortly after delivery (4). In 1959, vaccinia-like skin lesions were observed in a fetus aborted spontaneously at 4.5--5.0 months EGA; the mother was vaccinated at 9 weeks' EGA (6). In 1968, a premature infant born at 32 weeks' EGA to a mother who was vaccinated at 2 months' EGA had vaccinia-like scars but was otherwise healthy and developed normally (2). Affected pregnancies have been reported among women vaccinated in all three trimesters and among first-time vaccinees, revaccinees, and among unvaccinated close contacts of vaccinees (5). No validated prenatal test is available for clinical diagnosis of fetal vaccinia during pregnancy (2).

Except for fetal vaccinia, smallpox vaccine has not been clearly shown to cause serious birth defects or other adverse events for the fetus or neonate, including premature birth, low birthweight, or miscarriage (2). Among the general population, 16%--31% of pregnancies end in miscarriages; this rate is dependent on the gestational age of the pregnancy and other maternal risk factors (7,8). No evidence suggests that infants without fetal vaccinia born to exposed mothers have serious or chronic sequelae. Adverse maternal events have not been documented to occur more frequently after exposure to smallpox vaccine during pregnancy. Inadvertent exposure of pregnant women to smallpox vaccine should not be a reason to consider pregnancy termination because the risk for fetal vaccinia is low (2).

Because of the risk for fetal vaccinia and potential unknown risks to the fetus, smallpox vaccine is contraindicated during pregnancy unless a woman is exposed to smallpox. In the absence of exposure to smallpox, vaccine also should be deferred in women who might conceive within 4 weeks of vaccination and in persons who might have close contact with pregnant women within 4 weeks of their vaccination. CDC and ACIP recommend that all pre-event smallpox vaccination programs include pregnancy screening and education components with these elements: questioning about the possibility of pregnancy before vaccination and excluding those at risk, asking about the date of the last menstrual period, providing education about fetal vaccinia, counseling women to avoid becoming pregnant during the month after vaccination, recommending abstinence or highly effective contraception, and advising women who believe they might be pregnant to perform a first morning urine pregnancy test on the vaccination day (1).

Smallpox vaccination screening and education practices in the vaccination programs appear to be effective in deterring women who are pregnant and might not know it from receiving smallpox vaccine and in preventing pregnancy during the 4 weeks after smallpox vaccination. On the basis of the estimated number of pregnancies among the U.S. population of reproductive-aged women (9,10), CDC estimated the expected rate of unknown pregnancy (i.e., pregnancies of <4 weeks' gestation or <6 weeks based on obstetrical dating) and the estimated rate of conception during a 4-week period. In the general population, both the estimated rate of unknown pregnancy and the rate of conception during a 4-week period is six per 1,000 reproductive-aged women. Therefore, in the absence of screening and counseling, an estimated 12 per 1,000 reproductive-aged women vacinees could be expected to be exposed to smallpox vaccine during pregnancy. Assuming that health-care providers have the same age-specific fertility rates as the general population, when this rate is adjusted to the older age distribution of the civilian health-care workers currently vaccinated, an estimated four per 1,000 women would be pregnant and not know it and an additional four per 1,000 would be expected to conceive during the 4 weeks after vaccination. The rate of inadvertent exposure during pregnancy among women of reproductive age vaccinated during the first stage of the civilian and DoD programs is approximately one per 1,000. This rate is substantially lower than the approximately eight per 1,000 women and 12 per 1,000 women who would be inadvertently exposed to smallpox vaccine in the civilian health-care worker population and in the general population, respectively, in the absence of screening and education.

Because some women have been inadvertently exposed to smallpox vaccine during pregnancy, the U.S. military revised education materials for potential vaccinees and expanded the questions about pregnancy and intention to become pregnant on screening forms. FDA also has enhanced pregnancy screening materials and protocols. CDC is reviewing and evaluating existing recommendations for pregnancy screening and education in the civilian smallpox vaccination program. CDC continues to recommend that any woman who has pregnancy concerns take a pregnancy test on vaccination day, using her first morning urine. However, pregnancy tests might miss very early pregnancies and will not detect pregnancies conceived after vaccination. None of six reported exposures in the civilian program would have been prevented by urine pregnancy testing on the day of vaccination.

CDC, in collaboration with state health departments and FDA, is conducting a public health investigation to identify why civilian pregnant women have been inadvertently exposed to smallpox vaccines. DoD is undertaking a similar inquiry for military personnel. Information from these investigations is expected to guide efforts to improve the pregnancy screening and education components of the smallpox vaccination programs.

Health-care providers, state health departments, and other public health staff are encouraged to report all exposed pregnant women to the National Smallpox Vaccine in Pregnancy Registry. Civilian women should contact their health-care provider or state health department for help enrolling in the registry. Clinicians or public health staff should report civilian cases through their state health department or to CDC, telephone 404-639-8253 or 877-554-4625. Military cases should be reported to DoD, telephone 619-553-9255, DSN 553-9255, fax 619-553-7601 or e-mail [email protected]. mil. To better understand potential adverse events of smallpox vaccination during early pregnancy, health-care providers are encouraged to save and forward products of conception from pregnancy losses for vaccinia testing to CDC or DoD. Laboratories should freeze specimens at --94^º F (--70^º C), preferably in viral transport media. Clinicians can contact the registry for additional information about forwarding laboratory specimens.

This report is based on data contributed by state health departments, health-care providers, and women enrolled in the registry.

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Women with Smallpox Vaccine Exposure During Pregnancy Reported to the National Smallpox Vaccine in Pregnancy Registry --- United States, 2003

DoD Vaccination Program

Civilian Heath-Care and Public Health Workers

Clinical Studies

Editorial Note:

References

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