Current Trends Rubella Vaccination During Pregnancy -- United States, 1971-1981

Since 1971, CDC has maintained a register of women who received rubella vaccine within the 3 months before or after conception, and who were prospectively followed to quantitate the risk of fetal abnormalities following exposure to the vaccine.

From January 1971 to December 1981, 730 pregnant women who received rubella vaccine either within 3 months before or within 3 months after their presumed dates of conception were reported to CDC. Five hundred thirty-eight of these women received either Cendehill* or HPV-77** vaccines; 189 received RA 27/3((S)) vaccine, and three received rubella vaccine of an unknown type. At the time of vaccination, 215 women (29%) were known susceptible to rubella (no detectable rubella-specific antibodies); 42 (6%) were immune (presence of detectable rubella-specific antibodies), and 473 (65%) were of unknown immune status.

Exposure to Cendehill and HPV-77 vaccines (HPV-77:DE-5 and HPV-77:DK-12): The outcome of conception (live birth, stillbirth, spontaneous or induced abortion) was known for 500 of the 538 recipients of Cendehill or HPV-77 vaccines. Two hundred ninety (58%) of the vaccinees had full-term pregnancies (Table 1). None of the newborns had abnormalities compatible with congenital rubella syndrome (CRS)((P)). Eight infants born to susceptible mothers or to mothers whose immune status was unknown showed evidence of infection by detection of rubella-specific IgM in cord blood, by the persistence of rubella-specific hemagglutination inhibition (HI) antibodies beyond 6 months of age, or by the isolation of rubella virus. All eight children, who are now 2 to 7 years of age, are growing and developing normally with no demonstrated signs or symptoms of CRS.

Rubella virus was isolated from the products of conception in 17 of 85 (20%) susceptible women who had received Cendehill or HPV-77 vaccines and who elected to have abortions. Six spontaneous abortions were reported among the 100 susceptible women who had received these vaccines and whose pregnancies proceeded without intervention.

The dates of vaccination and the estimated dates of conception (DOC) were available for 87 of the 94 susceptible women who had full-term pregnancies (Figure 1). Of these, 33 (38%) were vaccinated within 1 week before to 4 weeks after conception. All women who carried their pregnancies to term gave birth to infants who did not have any malformations compatible with the CRS, regardless of interval between vaccination and conception.

Exposure to RA 27/3 vaccine: The outcome of pregnancy was known for 177 of the 189 recipients of the RA 27/3 vaccine. One hundred fifty-three (86%) of the vaccinees had full-term pregnancies (Table 2). None of the resulting newborns had abnormalities compatible with CRS. Serologic evaluation (rubella HI titers and specific IgM on cord or neonatal blood specimens) was performed for 44 of the 49 infants whose mothers were susceptible, and for 76 of the 89 infants whose mothers were of unknown immune status. One infant born to a susceptible woman had a rubella-specific IgM antibody titer of 8 in the cord blood. Both mother and infant had HI titers of 128 at the time of birth; the infant's HI titer decreased to 16 at 2 months of age. The infant had no evidence of malformations either at birth or at the 6 month followup examination.

Rubella virus was isolated from the products of conception in only 1 of 25 (4%) susceptible women studied who had received RA 27/3 vaccine within 3 months of conception (12 cases reported to CDC and 13 from the literature) (1-3). No spontaneous abortions were reported among the 49 susceptible women who had received RA 27/3 vaccine and whose pregnancies proceeded without intervention.

The dates of vaccination and estimated DOC were available for all of the 49 susceptible women who had full-term pregnancies (Figure 1). Twenty-one women (43%) were vaccinated within 1 week before to 4 weeks after conception. All women who had full-term pregnancies gave birth to infants who had no malformations compatible with CRS, regardless of interval between vaccination and conception. Reported by Immunization Div, Center for Prevention Svcs, CDC.

Editorial Note

Editorial Note: Since the licensure of live rubella virus vaccine in 1969, there has been concern that the attenuated vaccine virus poses teratogenic risks to the fetuses of pregnant recipients. A CDC register was set up to evaluate the risk; from that register, data are obtained through reports from physicians and state and local health departments, as well as directly from women vaccinated either within 3 months before or 3 months after conception. The patients are followed prospectively to determine the outcomes of the pregnancies.

During the highest risk period for viremia and fetal defects (1 week before to 4 weeks after conception) (4,5), 54 of the 143 (38%) susceptible mothers were vaccinated with one of the four vaccines. Neither these infants nor any of the others were born with CRS; therefore, the observed CRS risk to date is zero. The theoretical maximum risk for the occurrence of CRS in this group of children, based on the 95% confidence limits of the binomial distribution, may be as high as 3%. This overall maximum theoretical risk is far less than the 20% or greater risk associated with maternal infection with wild rubella virus during the first trimester of pregnancy (6).

In 1979, when RA 27/3 rubella vaccine replaced the other rubella vaccines, concern was raised that it might be more teratogenic than earlier rubella vaccines. Data from the CDC-maintained register thus far show no evidence that the RA 27/3 vaccine can cause defects compatible with CRS.

The 4% rubella virus isolation rate from products of conception for RA 27/3 vaccine is substantially lower than the 20% rate for the Cendehill and HPV-77 vaccines. Although limited, these data suggest there is probably no greater risk of placental or fetal infection from RA 27/3 vaccine than from Cendehill or HPV-77 vaccines (7).

Based on an earlier review of the data, the Immunization Practices Advisory Committee (ACIP) has stated that the risk of CRS following vaccination within 3 months of conception is so small as to be negligible (8). The additional data collected in 1981 support this statement. Rubella vaccination of a pregnant female should not in itself indicate abortion. A final decision, however, should rest with the patient and her physician.

Nevertheless, rubella vaccine should not be administered to pregnant females. Reasonable precautions before administering rubella vaccine to women of childbearing age include asking whether they are excluding those who are. Those who say they are not pregnant are advised not to become pregnant for 3 months after vaccination.

CDC encourages the reporting of all cases of rubella vaccination occurring within 3 months of conception so that the risks involved may be more completely defined for the presently licensed RA 27/3 vaccine. Laboratory services for serologic determination and for culture of abortion specimens are available at CDC for women who are entered on the register. Immunization Division personnel are available to discuss individual situations in detail.

References

1. Banatvala JE, O'Shea S, Best JM, Nicholls MV, Cooper K. Transmission of RA27/3 rubella vaccine strain to products of conception (letter). Lancet 1981;1:392.

2. Furukawa T, Miyata T, Kondo K, Kuno K, Isomura S, Takekoshi T. Clinical trials of RA 27/3 (Wistar) rubella vaccine in Japan. Am J Dis Child 1969;118:262-3.

3. Bernstein DI, Ogra PL. Fetomaternal aspects of immunization with RA27/3 live attenuated rubella virus vaccine during pregnancy. J Pediatr 1980;97:467-70.

4. O'Shea S, Parsons G, Best JM, Banatvala JE, Balfour HH Jr. How well do low levels of rubella antibody protect? (letter) Lancet 1981;2:1284.

5. Balfour HH Jr, Groth KE, Edelman CK, Amren DP, Best JM, Banatvala JE. Rubella viraemia and antibody responses after rubella vaccination and reimmunisation. Lancet 1981;1:1078-80.

6. Dudgeon JA. Congenital rubella. Pathogenesis and immunology. Am J Dis Child 1969;118:35-44.

7. Preblud SR, Stetler HC, Frank JA Jr, Greaves WL, Hinman AR, Herrmann KL. Fetal risk associated with rubella vaccine. JAMA 1981;246:1413-7.

8. ACIP. Rubella prevention. MMWR 1981;30:37-42, 47. *Distribution discontinued in the United States in December 1976 **Distribution discontinued in the United States in January 1979 ((S))Distribution begun in the United States in January 1979 ((P))Defined as any two complications listed in A or 1 from A and 1 from B

1. Cataracts/congenital glaucoma (either or both count as 1), congenital heart disease, loss of hearing, pigmentary retinopathy.

2. Purpura, splenomegaly, jaundice (with onset beginning 24 hours after birth), microcephaly, mental retardation, meningoencephalitis, radiolucent bone disease.

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