Risk Factor: CM
Class: Serums, toxoids, and vaccines/ Vaccines
Fetal Risk Summary
Rubella (German measles) vaccine is a live, attenuated virus vaccine (1,2). Animal reproduction studies have not been conducted with the vaccine.
Rubella occurring during pregnancy may result in the congenital rubella syndrome (CRS). The greatest risk period for viremia and congenital defects is 1 week before to 4 weeks after conception (3). Moreover, rubella reinfection, most often presenting as a subclinical infection that can be detected by a rise in antibody titers, may occur in previously vaccinated patients and in those who are naturally immune (4,5). The fetal risk of infection in these cases is low but has not yet been quantified.
The Centers for Disease Control and Prevention (CDC) defines CRS as any two complications from list A or one complication from list A plus one from list B (3): LIST A Cataracts or congenital glaucoma Congenital heart disease Loss of hearing Pigmentary retinopathy LIST B Purpura Splenomegaly Jaundice (onset within 24 hours of birth) Microcephaly Mental retardation Meningoencephalitis Radiolucent bone disease Before April 1979, the CDC collected data on 538 women vaccinated within 3 months before or after conception with either the Cendehill or HPV-77 vaccines (3). A total of 149 of these women were known to be susceptible at the time of vaccination and the outcome of pregnancy was known for 143 (96%). No evidence of CRS or other maternal or fetal complication was found in any of these cases or in an additional 196 infants exposed during pregnancy (3). Eight infants had serologic evidence of intrauterine infection after maternal vaccination, but follow-up for 27 years revealed no problems attributable to CRS.
Since January 1979, only RA 27/3 rubella vaccine has been available in the United States. In the United States between January 1979 and December 1988, a total of 683 women vaccinated with RA 27/3 have been reported to the CDC (6). The outcomes of these pregnancies were: Total vaccinated (1/7912/88)
A 2000 report described six women who received rubella vaccine (live, attenuated vaccine strain RA27/3) either in the pre- or periconceptional periods (8). No evidence of fetal infection was observed in five of the women. In one case, however, vertical transmission of the virus was documented that resulted in persistent fetal infection. The 25-year-old woman, unaware of her pregnancy, received the vaccine 3 weeks after conception. Virus isolation and polymerase chain reaction (PCR) of amniotic fluid obtained by amniocentesis at 16 weeks’ gestation confirmed the vertical transmission (8). Multiple maternal and fetal serologic and virologic testings were done throughout the pregnancy. Rising IgG titers and persistent IgM levels were measured in the fetus. At 39 weeks’ gestation, a cord blood sample was positive for virus isolation and PCR. Although a persistent rubella viral infection was documented, frequent monitoring of the pregnancy revealed no pathologic findings or complications and a healthy, 3450-g male infant was delivered at 40 weeks’ gestation. Apgar scores were 9, 9, and 10 at 1, 5, and 10 minutes, respectively. At 23 weeks of age, IgM, PCR, and virus isolation in his peripheral blood were negative. His growth and development have been normal up to 14 months of age (8).
Although no defects attributable to rubella vaccine have been reported, the CDC calculates the theoretical risk of CRS following vaccination with the RA 27/3 vaccine to range from zero to 1.6%, or from zero to 1.2% if data from all rubella vaccines are included (9). These risks are considerably lower than the 20% or greater risk associated with wild rubella virus infection during the 1st trimester (6). Because a theoretical risk does exist, the use of the vaccine in pregnancy is contraindicated (1,2 and 3,6,7,9). Moreover, both the manufacturer and the CDC recommend that women should avoid becoming pregnant for 3 months after receiving the vaccine (2,9). However, if vaccination does occur within 3 months of conception or during pregnancy, the actual risk, as stated above, is considered to be negligible and, in itself, should not be an indication to terminate the pregnancy (3,6,7,10,11).
Breast Feeding Summary
Vaccination of susceptible women with rubella vaccine in the immediate postpartum period is recommended by the American College of Obstetricians and Gynecologists and the CDC (1,9). A large number of these women will breast-feed their newborns. Although two studies failed to find evidence of the attenuated virus in milk, subsequent reports have demonstrated transfer (12,13,14,15 and 16).
In one case, the mother noted rash and adenopathy 12 days after vaccination with the HPV-77 vaccine on the 1st postpartum day (13). Rubella virus was isolated from her breast milk and from the infant’s throat (14). A significant level of rubella-specific cell-mediated immunity was found in the infant, but there was no detectable serologic response as measured by rubella hemagglutination inhibition antibody titers (14). No adverse effects were noted in the infant. In a second case report, a 13-day-old breast-fed infant developed rubella about 11 days after maternal vaccination with HPV-77 (17). It could not be determined whether the infant was infected by virus transmission via the milk (18,19). Nine (69%) of 13 lactating women given either HPV-77 or RA 27/3 vaccine in the immediate postpartum period shed virus in their milk (15). In another report by these same researchers, 11 (68%) of 16 vaccinated women shed rubella virus or virus antigen in their milk (16). No adverse effects or symptoms of clinical disease were observed in the infants.
- American College of Obstetricians and Gynecologists. Immunization during pregnancy. Technical Bulletin. No. 160, October 1991.
- Product information. Meruvax. Merck, 2001.
- CDC. Rubella vaccination during pregnancyUnited States, 19711982. MMWR 1983;32:42932.
- Burgess MA. Rubella reinfectionwhat risk to the fetus? Med J Aust 1992;156:8245.
- Condon R, Bower, C. Congenital rubella after previous maternal vaccination. Med J Aust 1992;156:882.
- CDC. Rubella vaccination during pregnancyUnited States, 19711988. MMWR 1989;38:28993.
- Preblud SR, Williams NM. Fetal risk associated with rubella vaccine: implications for vaccination of susceptible women. Obstet Gynecol 1985;66:1213.
- Hofmann J, Kortung M, Pustowoit B, Faber R, Piskazeck U, Liebert UG. Persistent fetal rubella vaccine virus infection following inadvertent vaccination during early pregnancy. J Med Virol 2000;61:1558.
- CDC. Measles, mumps, and rubellavaccine use and strategies for elimination of measles, rubella, and congenital rubella syndrome and control of mumps: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 1998;47(No. RR-8):157.
- Burgess MA. Rubella vaccination just before or during pregnancy. Med J Aust 1990;152:5078.
- Linder N, Ohel G. In utero vaccination. Clin Perinatol 1994;21:66374.
- Isacson P, Kehrer AF, Wilson H, Williams S. Comparative study of live, attenuated rubella virus vaccines during the immediate puerperium. Obstet Gynecol 1971;37:3327.
- Grillner L, Hedstrom CE, Bergstrom H, Forssman L, Rigner A, Lycke E. Vaccination against rubella of newly delivered women. Scand J Infect Dis 1973;5:23741.
- Buimovici-Klein E, Hite RL, Byrne T, Cooper LZ. Isolation of rubella virus in milk after postpartum immunization. J Pediatr 1977;91:93941.
- Losonsky GA, Fishaut JM, Strussenberg J, Ogra PL. Effect of immunization against rubella on lactation products. I. Development and characterization of specific immunologic reactivity in breast milk. J Infect Dis 1982;145:65460.
- Losonsky GA, Fishaut JM, Strussenberg J, Ogra PL. Effect of immunization against rubella on lactation products. II. Maternal-neonatal interactions. J Infect Dis 1982;145:6616.
- Landes RD, Bass JW, Millunchick EW, Oetgen WJ. Neonatal rubella following postpartum maternal immunization. J Pediatr 1980;97:4657.
- Lerman SJ. Neonatal rubella following maternal immunization. J Pediatr 1981;98:668.
- Bass JW, Landes RD. Neonatal rubella following maternal immunization (reply). J Pediatr 1981;98:6689.