From January 1971 through December 1985, 1,142 pregnant women who received rubella vaccine either within 3 months before or 3 months after their presumed dates of conception were reported to CDC. These women were followed prospectively to determine the risk of fetal abnormalities following exposure to the vaccine.

Cendehill and HPV-77 Vaccines. Before April 1979, data were collected on 538 women vaccinated during pregnancy with either Cendehill or HPV-77 rubella vaccine (1). The outcomes of conception--live birth, stillbirth, or spontaneous or induced abortion--were known for 143 (96%) of the 149 women known to be susceptible at the time of vaccination. Ninety-four (66%) of these 143 women carried their infants to term. All gave birth to infants free of defects compatible with congenital rubella syndrome (CRS) (2), although eight infants had serologic evidence of intrauterine infection (1,3). These eight children were all followed for at least 2 years, at which time all were growing and developing normally. The longest follow-up is for a child who is now 10H years old who had both an elevated rubella-specific immunoglobulin M (IgM) titer at birth and persistence of hemagglutination inhibition (HI) antibodies. Although he is still HI-antibody positive (he has not been vaccinated), he continues to grow and develop normally.

An additional 196 infants born to women who either were immune (22) or of unknown immune status (174) at the time of vaccination were also free of CRS-associated defects. Three other women (one susceptible, one immune, and one of unknown immune status) received unknown strains of rubella vaccine. All three delivered normal-appearing, healthy infants.

RA 27/3 Vaccine. Since licensure of the RA 27/3 rubella vaccine in January 1979, 614 pregnant women who received this vaccine during pregnancy have been reported to CDC (Table 3). Two hundred three (33%) of these 614 women were known to be susceptible at the time of vaccination. Outcomes of pregnancy are known for 191 (94%) of these susceptible women. Of the 191 women, 153 (80%) delivered 155 live infants. An additional 30 immune women and 319 women of unknown immune status delivered 350 live infants. All 505 infants were free of defects compatible with CRS.

The dates of vaccination and estimated dates of confinement were known for all 153 susceptible women who had full-term pregnancies (Figure 3). Fifty-three (35%) women were vaccinated within 1 week before to 4 weeks after conception, the period of presumed highest risk.

Serologic evaluations (rubella HI and specific IgM titers on cord or neonatal blood specimens) were performed on 121 (78%) of the 155 infants whose mothers were susceptible. One normal-appearing infant had a rubella-specific IgM antibody titer of 1:8 in cord blood and a corresponding HI titer of 1:128. The maternal titer was also 1:128. Retesting of cord blood and testing of a 2-month follow-up specimen run simultaneously showed a decline in HI antibody over the 2-month period from a titer of 1:64 to 1:16, suggesting that subclinical infection may not have occurred, since this pattern of decrease would be expected in maternally derived antibody. The infant had no evidence of defects compatible with CRS at birth or at the 18-month and 29-month follow-up examinations. Further follow-up sera could not be obtained to document persistence or disappearance of HI antibodies.

Blood studies were also obtained on 156 of the 320 infants born to mothers whose immune status was unknown at the time of vaccination. Subclinical infection was documented in two infants. One infant had a rubella-specific IgM antibody titer of 1:16 in cord blood. Both mother and infant had HI titers of 1:32 at the time of birth; the infant had a persistent HI titer of 1:32 at 4 months of age. This infant had no evidence of defects compatible with CRS at birth or at the 10-month and 17-month examinations. A serum specimen was not obtained at the follow-up visits. The second infant had a persistent HI titer of 1:8 at 3 months of age, suggesting that there had been subclinical infection. This infant was diagnosed as normal at the 3-month follow-up visit.

While none of the 155 infants born to susceptible women had defects compatible with CRS, two infants did have asymptomatic glandular hypospadias. However, both had negative rubella-specific IgM titers (less than 1:4) in cord blood at birth. A 6-month follow-up serum was available for one of the infants; he had a rubella HI antibody titer of less than 1:8 (i.e., a negative titer). Reported by Surveillance, Investigations, and Research Br, Div of Immunization, Center for Prevention Svcs, CDC.

Editorial Note

Editorial Note: Since 1971, CDC has maintained a register to monitor and quantitate the risks to the fetus following exposure to attenuated rubella vaccine virus. Data are obtained through reports from physicians and from 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 outcome of pregnancy. In 1979, when RA 27/3 rubella vaccine replaced the other rubella vaccines, concern was raised that it might have greater fetotropic and teratogenic potential than earlier vaccines. As with the other vaccines, data collected so far show no evidence that the RA 27/3 rubella vaccine can cause defects compatible with CRS.

Fifty-three (35%) of the 153 susceptible mothers were vaccinated with RA 27/3 vaccine during the presumed highest-risk period for viremia and fetal defects (1 week before to 4 weeks after conception) (4,5). None of their infants were born with CRS; therefore, the observed risk of CRS following rubella vaccination continues to be zero (Table 4). The theoretical maximum risk for the occurrence of CRS in this group of 155 children, however, based on the 95% confidence limits of the binomial distribution, could be as high as 2.4%. (If the 95 infants exposed to other rubella vaccines are included, the maximum theoretical risk is 1.5%.) This overall maximum risk remains far less than the 20% or greater risk of CRS associated with maternal infection with wild rubella virus during the first trimester of pregnancy (3) and is no greater than the 2%-3% rate of major birth defects in the absence of exposure to rubella vaccine (6).

These favorable data are consistent with the experiences in the Federal Republic of Germany and the United Kingdom (7,8). In neither country has the vaccine been associated with the occurrence of CRS among infants born to susceptible mothers who had been vaccinated. In Germany, 98 susceptible women vaccinated with either the Cendehill or RA 27/3 strain of vaccine gave birth to infants with no evidence of CRS. In the United Kingdom, one of 42 infants born to vaccinated mothers (rubella-immune status not specified) had pulmonic valve atresia but had no rubella-specific IgM or other serologic evidence of rubella infection.

The occurrence of any congenital defect following maternal vaccination deserves careful analysis and follow-up. In the U.S. series, two infants born to susceptible mothers had asymptomatic glandular hypospadias. While hypospadias has been noted in CRS cases (9,10), there are no data to suggest that glandular hypospadias should be considered a CRS-associated defect. In any case, neither of the two infants in question had serologic evidence of rubella virus infection. Ten other infants born to mothers of unknown immune status (eight) or known to be immune (two) at the time of vaccination had some type of defect (11). However, none of the defects were compatible with CRS, and serologic testing, when done, did not confirm rubella virus infection.

While no CRS-like defects have been noted, it is clear that rubella vaccine viruses, including the RA 27/3 strain, can cross the placenta and infect the fetus. Approximately 1%-2% of infants born to susceptible vaccinees had serologic evidence of subclinical infection, regardless of vaccine strain (3). On the other hand, while the rubella virus isolation rate from the products of conception for the RA 27/3 vaccine is only 3% (1/34), the rate of virus isolation for Cendehill and HPV-77 vaccines is 20% (17/85) (3). These data indicate that the risk of placental or fetal infection from RA 27/3 vaccine is minimal.

In view of the data collected through 1985, the Immunization Practices Advisory Committee (ACIP) continues to state that: (1) pregnancy remains a contraindication to rubella vaccination because of the theoretical, albeit small, risk of CRS; (2) reasonable precautions should be taken to preclude vaccination of pregnant women, including asking women if they are pregnant, excluding those who say they are, and explaining the theoretical risks to the others; and (3) if vaccination does occur within 3 months before or after conception, the risk of CRS is so small as to be negligible; thus, rubella vaccination of a pregnant woman should not ordinarily be a reason to consider interruption of pregnancy. The patient and her physician, however, should make the final decision (12).

CDC encourages reporting of cases to its register. Only cases involving women known to have been susceptible at the time of

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