Live Virus Vaccines

The live virus vaccines are those that raise the most concern during pregnancy. Many experts feel that they are categorically contraindicated during pregnancy. We certainly agree that these vaccines should be avoided during pregnancy whenever possible. Most of the time a trip can be postponed, or the disease-ridden areas avoided or exposure prevented by other means. When the vaccine is required simply for political reasons, a written waiver will usually suffice.

In our practice with pregnant travelers and expatriates, however, we find that there are instances when the travel cannot be delayed and exposure to these diseases cannot be prevented. Travel to yellow-fever endemic areas is such an example. A more extreme case would be a young woman who for various reasons has never before received even the routine childhood immunizations, is now assigned to work in an orphanage or refugee camp, and then finds out she is pregnant.

In these cases the literature would support the stance that the vaccines in question are safer for the pregnant woman and her fetus than are the diseases that these vaccines prevent. After obtaining the appropriate informed consent we will, in our practice, offer these vaccines. Below is the literature that we have found reassuring in these circumstances.

Yellow fever

1.
Suzano CE, Amaral E, Sato HK, Papaiordanou PM; Campinas Group on Yellow Fever Immunization during Pregnancy. The effects of yellow fever immunization (17DD) inadvertently used in early pregnancy during a mass campaign in Brazil. Vaccine. 2006 Feb 27;24(9):1421-6. Epub 2005 Oct 3. BACKGROUND: This study describes the consequences of the inadvertent immunization of pregnant women during a mass vaccination campaign in the Campinas region of the state of Sao Paulo, Brazil, in February and March 2000. The study was carried out by the Women's Comprehensive Healthcare Center (CAISM), at the State University of Campinas (UNICAMP). The objective of the study was to evaluate the possible effects of the vaccine on pregnancy and conceptus, and to assess congenital infection resulting from immunization. METHODS: Pregnant women who received the YF vaccine were identified at primary health clinics and referred to the study site, a public reference, high-risk clinic, serving 42 towns in a region with a population of 3,000,000. A 12-month serological follow-up for newborns (PRNT), and an examination to detect congenital abnormalities was offered to pregnant women, who signed a consent form. In a sub-sample of women who were delivered at the study site, additional exams were proposed: neonatal fontanel ultrasound, funduscopy, audiometry, neuro-pediatric follow-up until 12 months of age, and IgM detection at birth. Fifteen blood samples from placentas and umbilical cords were tested for PCR. FINDINGS: A total of 480 pregnant, immunized women were identified, who had received the vaccine at a mean of 5.7 weeks (95% CI 5.2-6.2) of gestation. The great majority of women were unaware of their pregnancy at the time they were vaccinated, and only 46.7% were counseled to avoid immunization if pregnant. After a minimum 6-week interval, 98.2% pregnant women were IgG positive. A total of 19.6% of women reported mild adverse events (headache, fever or myalgia). No IgM antibodies were detected at birth and no placental or umbilical cord blood was positive according to PCR. The frequency of malformations (2.3% or 7/304 babies), miscarriages (2.5% or 11/441 pregnancies), stillbirths (0.7%) and premature delivery (7.8%) was similar to that found in the general population. At 12 months follow-up, 7% of samples were reactive to PRNT. However, after 12 months, only one child was seropositive. INTERPRETATION: Contrary to a previous study, maternal seroconversion was very high when immunization was carried out in early pregnancy. Vaccine applied during the first trimester does not appear to cause malformations, complications to the central nervous system, nor adverse perinatal results as represented by premature deliveries or perinatal deaths. The 12-month serological follow-up is inconclusive and should be extended to 24 months. Evaluation of the risk of miscarriage was hindered by late presentation at the study clinic.

2.
Nasidi A. Yellow fever vaccination and pregnancy: a four-year prospective study. Trans R Soc Trop Med Hyg - 1993 May-Jun; 87(3): 337-9. During an outbreak of yellow fever (YF) in Nigeria in 1986-1987, women at various stages of pregnancy were vaccinated against YF, either because those pregnancies were not known at the time or because they requested vaccination out of fear of acquiring the disease. This offered an opportunity to assess the safety and efficacy of YF vaccine in pregnant women and the effect of this vaccine on their newborn children. Pre-vaccination and post-vaccination serum samples from the vaccinated pregnant women were tested by enzyme-linked immunosorbent assay and by neutralization tests for antibody to YF virus. The results showed that the antibody responses of these pregnant women were much lower than those of YF-vaccinated, non-pregnant women in a comparable control group. Follow-up of these women and their newborn children for 3-4 years showed no abnormal effect that could be attributed to the YF vaccine, which suggests that vaccination of pregnant women, particularly during a YF epidemic, may not be contraindicated.
3. Tsai TF, Paul R, Lynberg MC, et al: Congenital yellow fever virus infection after immunization in pregnancy. J Infect Dis 168:1520-1523, 1993. A case of congenital infection (with no clinical sequelae in the baby) demonstrated by IgM in cord blood. 40 other infants of vaccinated pregnant mothers had no IgM.
4. Yellow Fever Vaccine. Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2002 MMWR November 8, 2002 / Vol. 51 / No. RR-17
5. Monath TP. Yellow fever [Chapter 34]. In: Plotkin SA, Orenstein WA, eds. Vaccines. 3rd ed. Philadelphia, PA: W.B. Saunders, 1999;815–79 The safety of yellow fever vaccination during pregnancy has not been established, and the vaccine should be administered only if travel to an endemic area is unavoidable and if an increased risk for exposure exists.
6. Nishioka S de A, Nunes-Araujo FR, Pires WP, Silva FA,Costa HL. Yellow fever vaccination during pregnancy and spontaneous abortion: a case-control study. Trop Med Int Health 1998;3:29–33. OBJECTIVE: To assess a possible association between Yellow fever (YF) vaccine (inadvertently) administered during early pregnancy and spontaneous abortion. METHOD: A hospital-based case-control study conducted in a Brazilian town after a YF vaccine campaign that followed an epidemic of dengue. The study included 39 women who attended a university hospital with spontaneous abortion (cases) and 74 pregnant women attending the antenatal clinic of that hospital (controls). RESULTS: The crude odds ratio (relative risk estimate) of this association was 2.49, which dropped to 2.29 (95% CI 0.65-8.03) when adjusted for several confounders by multiple logistic regression. Dengue and exposure to organophosphate insecticide fogging during pregnancy were not associated with spontaneous abortion. CONCLUSION: This study, although small and with low power, provides some evidence that women vaccinated with YF vaccine during early pregnancy have an increased risk of having spontaneous abortion. Based on these findings a sensible recommendation should be to avoid YF vaccination of pregnant women unless their risk of acquiring YF outweighs the risk of vaccine-related abortion.
7. Monath TP, Cetron.MS, Prevention of Yellow Fever in Persons Traveling to the Tropics. Clinical Infectious Diseases 2002; 34:1369–78
8. Monath TP. Yellow fever: an update. Lancet Infectious Diseases 2001; 1: 11–20. Immunisation is contraindicated during pregnancy on theoretical grounds. Congenital infection appears to occur at a low rate (probably 1–2%) and has not been associated with fetal abnormalities
9. Robert E, Vial T, Schaefer C, Arnon J, Reuvers M. Exposure to yellow fever vaccine in early pregnancy. Vaccine 1999 Jan 21;17(3):283-5 We report on a data collection concerning exposure to yellow fever vaccine (YFV) during early pregnancy, ascertained through the European Network of Teratology Information Services (TISs) and the Pharmacovigilance Department of Pasteur Merieux Connaught (PMC). Six TISs had had no inquiry about YFV. Five submitted prospectively collected cases. Seventy-four cases were analyzed, 58 with a completed follow-up. Pregnancies ended in 46 births, five voluntary abortions and seven spontaneous abortions. Three newborns had minor anomalies and two had major defects (ureteral stenosis and triphalangeal hallux). Although the sample is too small to rule out a moderate increased risk of adverse reproductive effect of YFV, it gives no argument for such an effect and should lead to reassure pregnant women who might be inadvertently vaccinated
10. Suzano CE, Amaral E, Sato HK, Papaiordanou PM; The Campinas Group on Yellow Fever Immunization during Pregnancy. Vaccine. 2005 Oct 3 The effects of yellow fever immunization (17DD) inadvertently used in early pregnancy during a mass campaign in Brazil. INTERPRETATION: Contrary to a previous study, maternal seroconversion was very high when immunization was carried out in early pregnancy. Vaccine applied during the first trimester does not appear to cause malformations, complications to the central nervous system, nor adverse perinatal results as represented by premature deliveries or perinatal deaths. The 12-month serological follow-up is inconclusive and should be extended to 24 months. Evaluation of the risk of miscarriage was hindered by late presentation at the study clinic.

Rubella

1. Centers for Disease Control . Notice to Readers: Revised ACIP Recommendation for Avoiding Pregnancy After Receiving a Rubella-Containing Vaccine. MMWR 50(49):1117, 2001. Measles-mumps-rubella (MMR) vaccine and its component vaccines should not be administered to women known to be pregnant. Because a risk to the fetus from administration of these live virus vaccines cannot be excluded for theoretical reasons, women should be counseled to avoid becoming pregnant for 28 days after vaccination with measles or mumps vaccines or MMR or other rubella-containing vaccines.

Varicella

1. Shields KE, GalilK, Seward J, et al. Varicella vaccine exposure during pregnancy: Data from the First 5 Years of the Pregnancy Registry. Obstetrics & Gynecology July 2001, Volume 98, Number 1, Pages 14-19. Objective: To assess the risks of congenital varicella syndrome and other birth defects in offspring of women who inadvertently received varicella vaccine during pregnancy or within 3 months of conception. Methods: Pregnant women inadvertently exposed to varicella vaccine, reported voluntarily, were enrolled in the Pregnancy Registry for VARIVAX (Merck & Co., Inc., West Point, PA). The pregnancies were monitored and the outcomes ascertained from questionnaires completed voluntarily by the health care providers. The rates of congenital varicella syndrome and congenital anomalies were calculated for seronegative women prospectively reported to the registry. Results: From March 17, 1995 through March 16, 2000, 362 pregnancy outcomes were identified from prospective reports. Ninety-two women were known to be seronegative to varicella, of whom 58 received their first dose of vaccine during the first or second trimester. No cases of congenital varicella syndrome were identified among 56 live births (rate 0%, 95% confidence interval [CI] 0, 15.6). Among all the prospective reports of live births, five congenital anomalies were reported. No specific pattern was identified in either the susceptible cohort or the sample population as a whole. Conclusion: No abnormal features have been reported that suggested the occurrence of congenital varicella syndrome or other birth defects related to vaccine exposure during pregnancy. Because of the small numbers, this study has limited precision, so continued surveillance is warranted. However, these results should provide some assurance to health care providers and women with inadvertent exposure before or during pregnancy.

Smallpox

1. Suarez VR, Hankins GD. Smallpox and pregnancy: from eradicated disease to bioterrorist threat. Obstet Gynecol 2002 Jul;100(1):87-93