Canadian Immunization Guide
Seventh Edition - 2006

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Part 3
Recommended Immunization

Immunization in Pregnancy and Breast-Feeding

Introduction

Pregnancy provides a situation in which engagement in medical care may be greater than at any time in an otherwise healthy adult woman's life. It allows for evaluation of the woman's vaccine status as well as consideration of vaccines that may be beneficial to the neonate, if given to the woman, in order to decrease the risk of neonatal vaccine-preventable illness.

This chapter will review general issues regarding immunization in pregnancy, but particular issues will be addressed in vaccine-specific chapters. It is important that the obstetric care provider be familiar with both the potential risks of vaccination in pregnancy and the potential benefits in preventing disease at that time and providing neonatal protection. Ideally, this planning should occur before conception. If a woman of reproductive age presents with the intent to become pregnant, the adult immunization schedule should be reviewed and vaccines updated as indicated. For more information, please refer to the Recommended Immunization Schedules chapter.

Maternal benefits

Although pregnancy is an immunologically altered state, there are no data to support an inadequate response to vaccines. This is supported by data from trials of tetanus toxoid and polio vaccine in which normal adult immunologic responses were observed in pregnant women. There are a number of indications for immunization of pregnant women for the benefit of their own health. Recommendations include hepatitis B vaccine in a person with ongoing exposure risks, hepatitis A vaccine in a traveler or close contact of a person with hepatitis A, tetanus toxoid, meningococcal vaccine in an outbreak setting, and pneumococcal and influenza vaccines for all adult indications.

Maternal safety issues

There does not appear to be any evidence of increased risk of adverse reactions to vaccines administered in pregnancy. Reactions to vaccines in pregnancy are usually limited to local reactions, and no increase in anaphylactic reactions or events that might induce pre-term labour has been observed.

Safety and benefit of immunization in pregnancy for the fetus/infant

A major issue to consider regarding immunization in pregnancy is the risk or benefit of the vaccine for the fetus or neonate. There are no published data showing that any of the currently approved vaccines are teratogenic or embryotoxic, or have resulted in specific adverse pregnancy outcomes.

In contrast, there are a good deal of data supporting the beneficial effects of antenatal vaccines on the prevention of disease in the neonate. In order for a vaccine to be beneficial to a neonate, a protective concentration of maternal antibody needs to be transferred to the infant transplacentally. It is known that all subclasses of IgG are transported from mother to infant across the placenta, but the majority of transfer occurs during the third trimester. Active placental transfer of IgG is specific and has variable efficacy. The mechanism is not well understood but can result in a range of cord blood levels that can be 20% to 200% of maternal levels. Maternal IgG typically has a half-life of 3-4 weeks in the newborn, waning during the first 6-12 months of life. Current pediatric vaccine schedules take into consideration the potential effect that maternally transferred antibodies may have on infant vaccinations and incorporate this into the vaccine schedules and dosing.

Risks associated with vaccines in pregnancy are primarily theoretical risks associated with the administration of live virus vaccines. There are circumstances in which vaccination with a live-attenuated product may be considered (e.g., yellow fever vaccine). If live vaccine is inadvertently given to a pregnant woman, termination of the pregnancy is not recommended (see specific chapters for details).

Immunization in pregnancy: review of specific vaccine categories

1. Live-attenuated vaccines

In general, live-attenuated virus vaccines (such as measles, mumps and rubella (MMR) or varicella) are contraindicated in pregnancy as there is a theoretical risk to the fetus. However, it is important to mention that to date, there is no evidence to demonstrate a teratogenic risk from such vaccines.

• Rubella vaccine: please see the Rubella Vaccine chapter Rubella vaccine is available in combination with measles and mumps (MMR). It is a live attenuated vaccine and therefore contraindicated during pregnancy. The vaccine is indicated post-partum or pre-conception in susceptible women. It is advised that women should delay pregnancy by 1 month following such immunization. Inadvertent rubella vaccinations in pregnancy were reportable to the U.S. Centers for Disease Control and Prevention between 1971 and 1989. Analysis of the accumulated data revealed that subclinical infection was detected in 1%-2% of fetuses but that there was no evidence of congenital rubella syndrome in any of the offspring of 226 inadvertently vaccinated women. In addition, in a prospective study by Motherisk in Toronto, infants of 94 women immunized 3 months before conception or during pregnancy did not have an increased rate of malformation compared with an unexposed cohort. Termination of pregnancy should not be recommended following inadvertent rubella immunization on the basis of fetal risks. However, given the small theoretical fetal risk, immunization with the rubella vaccine is best delayed until after delivery. Breast-feeding and Rh immune globulin administration are not contraindications to immunization. Nevertheless, because of possible decreased immunogenicity of the vaccine in the presence of Rh immune globulin, it is recommended that rubella antibody status be checked at 2 months post-partum.
• Varicella vaccination: please see the Varicella Vaccine chapter Immunity to varicella should be reviewed in women of reproductive age, and vaccination should be recommended to non-pregnant women. Since the varicella vaccine is a live attenuated virus vaccine, its use should be avoided in pregnancy. A program to ensure that varicella vaccine is administered to the susceptible post-partum woman should be developed, with two doses given at least 4 weeks apart. In women receiving Rh immune globulin postpartum, an interval of 2 months should elapse before varicella vaccine is given. This is because of a theoretical risk of interference with immunogenicity. Breast-feeding is not a contraindication to vaccination nor is household contact with a newborn.In a study of 362 women, no cases of congenital varicella occurred as a result of inadvertent exposure to the vaccine in pregnancy. Inadvertent exposure to the vaccine, therefore, does not constitute a reason to recommend pregnancy termination. However, it is recommended that non-pregnant women who are vaccinated should delay conception by 1 month. Following exposure of a pregnant woman to varicella, a history of previous vaccination or of chickenpox illness should be sought, as it has been shown to correlate well with seropositive immune status. In the absence of such a history, the mother's immunity should be verified by testing for varicella IgG. Exposed susceptible women should be offered varicella immunoglobulin (VarIg) within 96 hours of exposure in an attempt to prevent the disease or reduce the severity of their infection. The recommended dosage is 125 IU for each 10 kg body weight up to a maximum of 625 IU. Although a study has shown that congenital varicella syndrome did not occur in the fetuses of 97 pregnant women given VarIg, this study is too small to conclude that VarIg will prevent or alter disease in the fetus (please refer to the Passive Immunizing Agents chapter for more specific recommendations). Susceptible pregnant women should be given varicella vaccine after delivery as long as 5 months have passed since VarIg administration.
• Other live attenuated vaccines: Other live attenuated vaccines must be evaluated on an individual risk/ benefit ratio. For instance, if a pregnant woman must travel to an area endemic for yellow fever, the vaccine may be administered when the risk of exposure is high and the travel cannot be postponed.

2. Inactivated viral and bacterial vaccines, toxoidsThere is no evidence to suggest a risk to the fetus or to the pregnancy from maternal immunization with these vaccines.

• Influenza vaccination:All pregnant women who are at high risk of influenza-related complications should be particularly targeted for influenza vaccination (see Influenza Vaccine chapter). Recent trends have indicated an increase in maternal age and higher rates of multiple gestation, both of which may present an increased risk of medical complications, including cardiorespiratory diseases, that would warrant influenza vaccination as per the adult indications. There is some evidence, although limited, suggesting that healthy pregnant women are at increased risk of complications from influenza. Mortality rates among pregnant women in the 1918 and 1957 pandemics were reported to be as high as 45%. This is presumably because pregnancy is associated with significant cardiovascular and respiratory demands, with increased stroke volume, heart rate and oxygen consumption. A more recent report demonstrated that the need for hospitalization was 4 times greater in pregnant than non-pregnant women with influenza. The risks were, in fact, calculated to be equivalent to those of non-pregnant women with high-risk conditions for whom immunization has traditionally been recommended.However, given these limited data, more research is needed to clarify the feto-maternal advantages of influenza vaccine. The data regarding safety of the vaccine appear to be reassuring. A study of 252 pregnant women vaccinated during pregnancy at a mean gestational age of 26.1 weeks (range 14-39 weeks) had no adverse events and no difference in perinatal outcomes compared with a non-vaccinated group.

Immunization and breast-feeding

Breast-feeding is considered safe following immunization of the mother and has not been shown to adversely influence the maternal immune response. Therefore, breast-feeding does not represent a contraindication to any maternal immunization, and breast-feeding women who have not received all recommended adult immunizations may be safely immunized. Infants who are breast-fed should receive all recommended vaccines at the usual times.

Passive immunization

There is no known risk to the fetus and/or mother from administration of immune globulin for passive immunization during pregnancy. Therefore, these products should be administered as required.

Table 7. Indication for Use in Pregnancy

Selected references

Bar-Oz B, Levichek Z, Moretti ME et al. Pregnancy outcome following rubella vaccination: a prospective controlled study. American Journal of Medical Genetics 2004;130(1):52-4.

Centers for Disease Control and Prevention. Measles, mumps and rubella vaccine 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). Morbidity and Mortality Weekly Report 1998;32(RR-8):32.

Freeman DW, Barno A. Deaths from Asian influenza associated with pregnancy. American Journal of Obstetrics and Gynecology 1959;78:1172-75.

Harris JW. Influenza occurring in pregnant women: a statistical study of thirteen hundred and fifty cases. Journal of the American Medical Association 1919;72(978):980.

Kanariou M, Petridou E, Liatsis M et al. Age patterns of immunoglobulins G, A and M in healthy children and the influence of breast feeding and vaccination status. Pediatric Allergy and Immunology 1995;6(1):24-9.

Munoz FM, Greisinger AJ, Wehmanen OA et al. Safety of influenza vaccination during pregnancy. American Journal of Obstetrics and Gynecology 2005;192(4):1098-1106.

Neuzil KM, Reed GW, Mitchel EF et al. Impact of influenza on acute cardiopulmonary hospitalizations in pregnant women. American Journal of Epidemiology 1998;148(11):1094-1102.

Pabst HF, Godel J, Grace M et al. Effect of breast-feeding on immune response to BCG vaccination. Lancet 1989;1(8633):295-97.

Pabst HF, Spady DW. Effect of breast-feeding on antibody response to conjugate vaccine. Lancet 1990;336(8710):269-70.

Shields KE, Galil K, Seward J et al. Varicella vaccine exposure during pregnancy: data from the first 5 years of the pregnancy registry. Obstetrics and Gynecology 2001;98(1):14-9.

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