Keywords

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FormalPara Key Points

  • Pregnant women are relatively immune-suppressed, so:

    • Live vaccines are generally contraindicated.

    • Vaccines may have suboptimal effects.

  • Inactivated viruses and bacterial vaccines and toxoid vaccines are considered safe.

  • Pregnant women should receive influenza- and pertussis-containing vaccines.

  • Delay vaccinations until the second or third trimester when possible.

  • Make an individualised risk assessment based on safety and efficacy of vaccine and the actual risk of exposure.

General Considerations

One of the goals of maternal vaccination is the protection of the infant against infectious diseases. Many times, the most effective way of protecting the unborn and newly born infant is to immunise the mother. Many antibodies can be passed transplacentally to the infant and thus provide a level of protection prior to and immediately after birth. The primary goal of vaccination during pregnancy is, of course, to protect the mother (Table 11.1).

Table 11.1 Immunisations in pregnancy
Full size table

Because controlled studies are not carried out on pregnant women, data is not available regarding individual vaccines in pregnancy. However, there are no known significant risks involved in vaccinating pregnant women with inactivated virus or bacterial vaccines or toxoids. Live vaccines may pose a theoretical risk to the fetus. The benefits of vaccinating pregnant women usually outweigh potential risks when the likelihood of disease exposure is high and unavoidable and when infection would pose a risk to the mother or fetus. When feasible, the itinerary may need to be modified to avoid the risk of exposure to the disease.

Immunologic changes that occur during pregnancy, however, may in some cases dampen the immune response that one wishes to obtain by these vaccines. This has been seen to some extent with yellow fever vaccination and perhaps also with hepatitis B vaccination.

If possible, vaccination should be delayed until the second or third trimester, to avoid possible teratogenic febrile effects during the first trimester.

Toxoids

Tetanus, Diphtheria and Pertussis Vaccines (Tdap)

Tetanus, diphtheria and pertussis vaccines are ones that are recommended for all pregnant women if they are not already immune. It is generally recommended that the combined vaccine be given during the third trimester of pregnancy to provide maximum benefit to both the mother and infant. There has been some concern that malnutrition, vitamin A deficiency or malaria chemoprophylaxis might interfere with an adequate immune response; therefore, the vaccine should be given whenever possible before the initiation of malaria chemoprophylaxis.

Tuberculin Skin Testing

Mantoux testing, if indicated, is safe in pregnancy and interpreted according to the same criteria as in the non-pregnant.

Polysaccharide, Killed Bacterial and Conjugate Vaccines

Pneumococcal

Morbidity from pneumonia is increased in pregnancy, largely due to respiratory and cardiovascular changes. Premature labour and fetal death may result from this. Thus, any recommendation for the use of pneumococcal vaccine is not altered by pregnancy. Patients and travellers, who might be considered for this vaccine, would include those who are immunosuppressed, have had a splenectomy or have sickle cell disease. Maternal vaccination has been shown to increase milk concentrations of IgA antibodies, so there is benefit to the newborn as well.

Meningococcal

Studies of polysaccharide vaccine (MPSV4: quadrivalent meningococcal polysaccharide vaccine) use during pregnancy have not demonstrated adverse effects among either pregnant women or newborns. The available data regarding the use of the conjugate (MCV4: quadrivalent meningococcal) vaccine during pregnancy have shown no vaccine-related ill effects.

Typhoid

Typhoid may be a more serious disease in pregnancy, with a higher incidence of complications such as bleeding intestinal ulcers. There is also an increased risk of abortion and fetal death. Transplacental infection of the fetus may also occur. Typhoid vaccination is recommended whenever it might otherwise be indicated. Both the injectable and the oral forms of vaccine are considered acceptable during pregnancy, but due to the slowing of gastrointestinal function and resulting side effects, the injectable form might be preferred. With either vaccine, no more than 70 % efficacy can be expected; thus, food and water precautions remain important.

Inactivated Virus Vaccines

Hepatitis A

Hepatitis A infection during pregnancy may result in serious maternal consequences with fetal loss or vertical transmission to the fetus; therefore, vaccination during pregnancy is recommended.

Hepatitis B

In the case of hepatitis B, the danger of the disease lies in the risk of transmission to the infant. While there is some evidence of a lower antibody response in pregnancy, vaccination of pregnant women with this vaccine has been shown to be safe and effective and is recommended in nonimmune women.

Influenza

Influenza results in increased morbidity and mortality during pregnancy. Vaccination with the inactivated influenza vaccine is now recommended for all pregnant women at any stage of pregnancy.

Polio

This disease, should it occur during pregnancy, may result in as high as a 40 % neonatal mortality, and there is an increased risk of maternal paralytic disease in pregnancy. The enhanced inactivated polio vaccine (eIPV) is preferred for its safety both in the pregnant patient and in the community. The live oral polio vaccine (OPV) is no longer available in most countries and is considered contraindicated in pregnancy, but there are reports of pregnant women having received it with no evidence of fetal or maternal harm.

Japanese Encephalitis

The Japanese encephalitis virus causes embryo-fetal death in experimental animals and has been known to be passed transplacentally. The cell-derived, inactivated Jespect®/Ixiaro® vaccine would theoretically be safe in pregnancy. The live vaccine is contraindicated. Despite the lack of available data, due to severe consequences of the disease, it would seem prudent to vaccinate pregnant women for whom exposure is likely. Mosquito avoidance should, however, remain the mainstay of prevention.

Rabies

Because rabies is almost universally fatal, the consensus has long been that postexposure rabies vaccination should be used during pregnancy when indicated. There is presumptive evidence of transplacental passage of antibodies. This supports the use of pre-exposure vaccination when there is a substantial risk of maternal exposure to the disease.

Human Papilloma Virus (HPV)

Recent data hint that there may be an association between high-risk HPV and pre-eclampsia. This plus the fact that many travellers become exposed to sexually transmitted diseases makes us consider this vaccine in counselling pregnant travellers. The HPV vaccine contains inactivated virus and thus is considered safe in pregnancy. Another consideration recommending the use of this vaccine during pregnancy is the vertical transmission of the virus to the fetus at the time of birth.

Tick-Borne Encephalitis

The virus may be transmitted transplacentally, but there is little data on the consequences of this. There have been reports of high fever after the administration of the vaccine to young children, but this does not seem to be as common in adults. The manufacturers recommend its use in pregnancy only after careful, individual consideration.

Live Virus Vaccines

It is primarily the viral illnesses such as rubella and varicella that have shown the propensity to cause recognisable patterns of fetal damage if they occur during pregnancy. Thus, there is added reason to protect against these viruses during pregnancy. But the vaccines available for such protection are live viruses, altered from their original teratogenic form but with the theoretical potential nonetheless of causing the very pattern of birth defects that they are designed to prevent. Several decades of available data on inadvertently administered vaccine are somewhat reassuring, but these vaccines should be avoided during pregnancy wherever possible.

Mumps

Some spontaneous abortions and other fetal anomalies have been reported when this disease occurs in the first trimester. In the rare event that exposure to this disease is likely to occur in a nonimmune pregnant woman, administration of the vaccine would be considered preferable to contracting the disease.

Measles

Available data would seem to indicate an increased rate of abortion as well as a perinatal mortality rate of 10 % and possibly fetal anomalies if the disease is contracted during pregnancy. There is also the risk of serious maternal complications, particularly pneumonia and fetal loss, if this disease occurs during pregnancy. As with the mumps vaccine, no adverse maternal or fetal events have been reported following the inadvertent administration of this vaccine during pregnancy.

Rubella

This is probably the most feared viral infection during pregnancy. Pre-vaccine statistics showed an almost 100 % incidence of congenital rubella syndrome (CRS) if the disease is contracted in the first trimester and up to 60 % in the second trimester.

Despite careful observation, no such syndrome has been seen to occur with vaccination, even though there is evidence of passage of the vaccine virus to the fetus. If there is risk of rubella infection in a nonimmune pregnant woman, use of the vaccine is felt to be preferable to contracting rubella during the pregnancy. It should be noted that about 2 % of women do not respond with sufficient antibody production to develop immunity. Rubella immune globulin may be considered as an alternative postexposure prophylaxis, but there is very little data to support its efficacy.

Varicella

As with rubella, there is a risk of a syndrome of congenital defects associated with maternal varicella infection, and this disease can have serious maternal and fetal consequences if contracted late in pregnancy. For susceptible pregnant individuals with unavoidable likely exposure to this virus, the vaccine would be considered preferable to the disease. As with rubella, one may consider the use of postexposure varicella immune globulin, but its efficacy remains unproven.

Herpes Zoster

Herpes zoster (shingles) is not known to be more common or more severe during pregnancy, but it may have serious fetal effects. Because the zoster vaccine contains a significantly larger dose of virus than the routine varicella vaccine, however, its use in pregnancy is not advised.

Yellow Fever

Yellow fever is a very serious disease with up to 50 % mortality rate in native populations and thus needs to be avoided during pregnancy. There is reassuring data from several sources regarding the safety of this vaccine during pregnancy.

Meanwhile, the efficacy data is conflicting, with some data showing a lower antibody titre when this vaccine is given during pregnancy. The relative immune suppression that occurs with pregnancy or a difference in nutritional status might explain this difference. Even the lower titres, however, were not correlated with any diminished protectiveness of the vaccine. The consensus remains that if yellow fever exposure is likely and unavoidable during the travel, the vaccine should be given. Under these circumstances, however, it might be wise to obtain a titre to test for immunity. If travel requirements and no disease exposure are the only reason to vaccinate, then it would be preferable to provide the pregnant traveller with an appropriate waiver.

Live Oral and Bacterial Vaccines

BCG

Tuberculosis is a serious disease even in pregnancy. The BCG vaccine, however, is of limited value in adulthood. Although no harmful effects to the fetus have been associated with BCG vaccine, disseminated infections with other mycobacteria have been reported in the infants of infected mothers, and so its use, being a live bacterium, is not recommended during pregnancy.

Typhoid

When speaking of typhoid vaccine, some recommend the preferential use of live, oral vaccine. There is at least a theoretical risk, however, that the vaccine strains might replicate and cross the placental barrier, causing fetal harm similar to that seen with Salmonella typhi. In addition, decreased gastrointestinal motility along with increased exposure to gastric acid might either decrease the vaccine’s effectiveness or enhance the risk of gastroenteritis. Also, one of the more common side effects of this vaccine is nausea and vomiting, a problem already frequent in pregnancy. These considerations might make the use of the Typhim Vi® vaccine preferable during pregnancy.

Cholera and Traveller’s Diarrhoea

Recent studies point out the severe risk that cholera presents during pregnancy. Traveller’s diarrhoea is also likely to be more frequent and more severe in pregnancy. To date, the benefit from the available vaccines has been found to be short-lived and incomplete, and they are not usually recommended except when the traveller will be working in high-risk areas such as refugee camps. Dukoral® as an inactivated vaccine is probably safe to use in pregnancy, but as with the oral typhoid vaccine, the side effects of nausea and vomiting may reduce its benefit in an already nauseated pregnant patient.

Immune Globulin

Generally, the immune globulins are felt to be safe in pregnancy, but because the immune globulins are a human blood product, the possibility of inadvertent disease transmission remains. There remain conditions, however, such as varicella and rabies where postexposure use of these products is highly recommended, even in pregnancy.

Unusual Vaccines

These are vaccines of various types which are not in common use but the need for which might arise under special circumstances.

Anthrax

At least one review estimates that this disease predisposes to miscarriage and preterm delivery. Most experts primarily recommend various medications for postexposure prophylaxis. In a study of women who became pregnant shortly after receiving the vaccine, there was no increased incidence of adverse pregnancy outcomes.

Smallpox

The vaccine is prepared from vaccinia virus, a virus that occurs only in the laboratory. Infection with this virus has been reported in the fetus after maternal immunisation. Thus, the administration of smallpox vaccine is not recommended during pregnancy.

Brucellosis

Brucellosis is known to cause abortion and preterm delivery in domestic animals and to a lesser degree in humans. Vaccination against this disease is usually limited to persons in high-risk occupations. Prophylactic or treatment doses of co-trimoxazole or rifampin are recommended instead of the vaccine.