Recombinant or killed virus vaccines

Some of the vaccines in this category are commonly used in pregnancy regardless of travel plans. We provide these references in support of their routine use. Special caution is advised, however, with the use of Japanese Encephalitis vaccine simply because it has a potential side effect profile that can be quite severe even in the non-pregnant state.
Influenza

1. Neuzil KM, Griffin MR, Schaffner W. Influenza Vaccine: Issues and Opportunities. Infectious Disease Clinics of North America Volume 15 • Number 1 • March 2001. Several recent developments offer opportunities to improve the diagnosis, treatment, and prevention of influenza. Rapid diagnostic tests assist in selecting patients for antiviral therapy and avoid some antibiotic use. The neuraminidase inhibitors now offer therapeutic options with potentially fewer side effects than the traditional drugs, albeit at greater cost. Inactivated influenza vaccine is now recommended annually for all persons aged 50 and older and younger adults and children (aged 6 months and older) who have underlying risk factors for the severe complications of influenza. This includes pregnant women who are in their second or third trimesters during influenza season.
2. Yeager DP, Toy EC, Baker B 3rd. Influenza vaccination in pregnancy. Am J Perinatol 1999;16(6):283-6 The objective of this paper is to determine the acceptance rate of and incidence of adverse reactions to the influenza vaccine in pregnant women, and to determine the immunized patients' attitudes toward future vaccination. A total of 448 eligible pregnant women were offered the influenza vaccine at routine prenatal visits. Vaccinated women were interviewed at their subsequent visit regarding adverse effects and attitudes toward future vaccination. Of the 448 women studied, 319 (71.2%) accepted the vaccine. There was no difference in acceptance rates between English- and Spanish-speaking women. Mild adverse reactions were experienced by 5.3%. Women who reported adverse reactions were less likely to agree to future vaccination as compared with unaffected women (64.7 vs. 94.0% p < 0.001). The influenza vaccine is readily accepted by pregnant women, and is infrequently associated with mild side effects. Women who experience side effects are less likely to accept the vaccine in the future.
3. Neuzil KM, Reed GW, Mitchel EF, Simonsen L, Griffin MR. Impact of influenza on acute cardiopulmonary hospitalizations in pregnant women. Am J Epidemiol 1998 Dec 1;148(11):1094-102. This study sought to quantify influenza-related serious morbidity in pregnant women, as measured by hospitalizations for or death from selected acute cardiopulmonary conditions during predefined influenza seasons. The study population included women aged 15-44 years who were enrolled in the Tennessee Medicaid program for at least 180 days between 1974 and 1993. In a nested case-control study, 4,369 women with a first study event during influenza season were compared with 21,845 population controls. The odds ratios associated with study events increased from 1.44 (95% confidence interval (CI) 0.97-2.15) for women at 14-20 weeks' gestation to 4.67 (95% CI 3.42-6.39) for those at 37-42 weeks in comparison with postpartum women. A retrospective cohort analysis, which controlled for risk factors identified in the case-control study, identified 22,824 study events during 1,393,166 women-years of follow-up. Women in their third trimester without other identified risk factors for influenza morbidity had an event rate of 21.7 per 10,000 women-months during influenza season. Approximately half of this morbidity, 10.5 (95% CI 6.7-14.3) events per 10,000 women-months, was attributable to influenza. Influenza-attributable risks in comparable nonpregnant and postpartum women were 1.91 (95% CI 1.51-2.31) and 1.16 (95% CI -0.09 to 2.42) per 10,000 women-months, respectively. The data suggest that, out of every 10,000 women in their third trimester without other identified risk factors who experience an average influenza season of 2.5 months, 25 will be hospitalized with influenza-related morbidity.

Hepatitis B

1. Grosheide PM, Schalm SW, van Os HC, Fetter WP, Heijtink RA. Immune response to hepatitis B vaccine in pregnant women receiving post-exposure prophylaxis. Eur J Obstet Gynecol Reprod Biol 1993 Jun;50(1):53-8. Hepatitis B immunoglobulin and vaccine were given as post-exposure prophylaxis to 73 women after an outbreak of hepatitis B due to in vitro fertilization treatment. The immunization schedule consisted of 5 ml of hepatitis B immunoglobulin (125 IU/ml) at months 0 and 1 and recombinant hepatitis B vaccine (10 micrograms of HBvaxDNA) at months 0, 1, 2 and 6. The safety and immunogenicity of hepatitis B vaccine were studied in 16 women who became pregnant after in vitro fertilization; 57 non-pregnant women receiving the same treatment served as controls. Blood samples were drawn at 0, 1, 2, 6 and 7 months. One patient had a clinical abortion 2 days after initial immunization; other side effects of vaccination were not found in vaccinees or in their offspring. All vaccinees exhibited antibodies against hepatitis B surface antigen after vaccination but relatively low peak geometric mean titers of 258 IU/l and 684 IU/l were attained in pregnant and non-pregnant women, respectively. There were no significant differences in seroconversion rates and geometric mean titers between the two groups although the immune response to hepatitis B vaccine was slower and lower in pregnant women at all times. Our results suggest that when post-exposure prophylaxis for hepatitis B infection is indicated, passive active immunization can be started safely during pregnancy. The relative weak response to the vaccine calls for monitoring of the anti-HBs 1 month after the initial series of vaccinations.
2. Ayoola EA, Johnson AO. Hepatitis B vaccine in pregnancy: immunogenicity, safety and transfer of antibodies to infants. Int J Gynaecol Obstet 1987 Aug;25(4):297-301. To determine the safety and immunogenicity of hepatitis B vaccine in pregnancy, 72 pregnant Nigerians who were negative for markers of hepatitis B virus (HBV) were given two intramuscular doses of vaccine (Heptavax, Merck) in the third trimester. One month after the second dose (at T2), 84% were anti HBs positive. No significant effect was observed in the mothers or their newborns. Passive transfer of anti HBs occurred in 59% of the newborns. The antibodies disappeared rapidly in these infants and by 3 months only 23% had detectable antibodies. No HBsAg carrier status developed in this group. In contrast, the infants born to HbsAg positive mothers had a cummulative rate of HBV events of 20%. It is concluded that HBV vaccine is safe and immunogenic in pregnant females. The passive immunity conferred on the infants is of short duration. Therefore, infants in endemic areas should be vaccinated early, preferably within 3 months of birth. Vaccination of pregnant mothers may provide adequate protection before the child is vaccinated.

3. World Health Organization, International Travel and Health, 2002 Chapter 6

Hepatitis A

1. Duff B, Duff P. Hepatitis A vaccine: ready for prime time. Obstet Gynecol. 1998 Mar;91(3):468-71. Two new inactivated hepatitis A vaccines are available that confer long-term protection against infection. They are indicated for pre-exposure prophylaxis in persons older than 2 years of age. For one vaccine preparation, Vaqta (Merck and Co., West Point, PA), the recommended schedule for adults is a 1.0-mL (50 U of hepatitis A viral antigen) intramuscular dose initially, followed by a booster dose 6-12 months later. Children 2-17 years of age should receive 0.5 mL (25 U of hepatitis A viral antigen) initially, followed by a booster dose 6-18 months later. The adult dosage schedule for Havrix (SmithKline Beecham, Philadelphia, PA) is a 1.0-mL (1440 enzyme-linked immunosorbent assay [ELISA] units) intramuscular dose initially, followed by a 1.0-mL booster dose 6-12 months later. Patients 2-18 years of age should receive doses of 0.5 mL (720 ELISA units). Primary candidates for vaccination are travelers to regions of endemic disease, children living in high-prevalence areas, homosexual males, users of illicit intravenous drugs, persons working directly with nonhuman primates or hepatitis A virus, patients older than 30 years of age with chronic liver disease, and persons who have received a liver transplant or are awaiting one. Seroconversion rates in healthy children and adults exceed 95%. Both vaccines are safe for use in pregnancy.

Rabies

1. Fescharek R, Quast U, Dechert G. Post exposure rabies vaccination during pregnancy. Vaccine 1990;8:409. The cell culture rabies vaccines may be given during pregnancy for either pre- or postexposure prophylaxis. A 1991 review of the literature cited 24 cases of pregnant women exposed to rabid animal bites.
2. Chabala S, Williams M, Amenta R, Ognjan AF. Confirmed rabies exposure during pregnancy: treatment with human rabies immune globulin and human diploid cell vaccine. Am J Med 1991;91:423–424. Exposures occurred during all trimesters. The women received equine rabies immune globulin and/or vero cell vaccine or duck embryo vaccine. There was one fatality due to inappropriate postexposure prophylaxis. Among the infants, two were born prematurely, and there was one spontaneous abortion. There were no physical or mental abnormalities except in the case described where the child did well after repair of transposition of the great vessels. In this child, the bite occurred weeks after the heart formed embryologically

Japanese encephalitis

We have been unable to find any studies pertinent to the use of Japanese Encephalitis vaccine during pregnancy. The manufacturer states that no animal studies have been done but lists the vaccine as "Pregnancy Category C." Because of potentially serious and delayed adverse effects from this vaccine, we use it in pregnancy only with those special precautions listed in the package insert.