Vaccination During Pregnancy
Introduction
Infectious diseases during pregnancy can affect not only the health of the pregnant woman but also that of the fetus. Vaccinating a pregnant woman can protect both the mother and the fetus and newborn. Due to passive immunity, maternal IgG immunoglobulins transferred across the placenta appear in the fetal blood from the second trimester of pregnancy. The concentration of these antibodies increases particularly rapidly during the last 2 months of pregnancy. If the mother has no antibodies, the newborn will not receive them either. Ideally, a woman should be vaccinated before pregnancy; however, in certain situations, active immunoprophylaxis can also be used during pregnancy. The main principle of vaccination during pregnancy is based on assessing the risk of infectious disease to the mother and fetus and comparing it with the potential harm caused by the vaccine. In recent years, increasing attention has been given to vaccinating pregnant women with non-live vaccines to ensure protection of newborns during the first months of life, when the newborns themselves cannot yet be vaccinated. Vaccination during pregnancy is effective despite the fact that the woman's immune system adapts to the genetically distinct fetus.
Non-live vaccines can be safely administered to pregnant women, whereas live vaccines are contraindicated. The 2016 recommendations of the U.S. Centers for Disease Control and Prevention (CDC) state that tetanus, diphtheria, pertussis, and influenza vaccines are recommended during pregnancy. These vaccines are safe and can be administered during any trimester of pregnancy. Vaccinating the mother provides immunity to the newborn, and there is no evidence that administration of these vaccines increases the risk of miscarriage. It is particularly important to vaccinate pregnant women who are more likely to encounter infected individuals or contaminated environments and who could avoid disease through vaccination. After delivery, a previously unvaccinated woman is advised to receive vaccines that cannot be administered during pregnancy (e.g., measles, mumps, and rubella and varicella vaccines).
Types of Vaccines and Vaccination During Pregnancy
All inactivated vaccines and immunoglobulin preparations can be administered to pregnant women because there is no evidence that they have adverse effects on the mother or fetus. When medically indicated, these vaccines can be administered at any stage of pregnancy, including the first trimester, because the risk of harm caused by infection is considerably greater than that posed by the vaccine. For example, seasonal influenza vaccination is recommended before the beginning of the influenza season, regardless of the stage of pregnancy. In other cases, vaccination may be postponed until the second trimester because immunization between 28 and 32 weeks of pregnancy results in the transfer of the greatest amount of protective antibodies to the fetus.
When a live attenuated vaccine is administered to a pregnant woman, there is a theoretical risk that the microorganisms used to produce the vaccine may mutate into their original pathogenic form, cause disease, and infect the fetus. Therefore, live vaccines should not be administered to pregnant women, except in cases where the risk of a particularly dangerous infectious disease is much greater than the risk of complications following vaccination (e.g., when there is a risk of yellow fever infection). If a pregnant woman has been vaccinated with a live vaccine or becomes pregnant within 4 weeks after vaccination, she should be monitored, but termination of pregnancy is not recommended.
It is important to explain to pregnant women that they should avoid contact with infected individuals or contaminated environments and avoid traveling to countries where there is an increased risk of serious infectious diseases such as yellow fever and poliomyelitis. Family members of pregnant women should also receive the recommended vaccines, and older children should be vaccinated according to the national childhood vaccination schedule. This would provide comprehensive protection against vaccine-preventable infections for both the pregnant woman and her newborn.
Vaccination Before Pregnancy
Ideally, women of childbearing age should receive all recommended vaccines (tetanus, diphtheria, pertussis, measles, mumps, rubella, varicella, influenza, and tick-borne encephalitis) before pregnancy. This could help prevent infections that may harm both the mother and the fetus. Women of childbearing age who are planning pregnancy should ensure that they have developed immunity to measles, rubella, mumps, and varicella. Immunity is determined by detecting IgG-class antibodies. IgM-class antibodies are tested only when an acute infection is suspected. Before administering the aforementioned live vaccines, it should be confirmed that the woman is not pregnant and is not planning to become pregnant within the next 4 weeks.
The woman should be informed about the potential risks of live vaccines to pregnancy when vaccination is performed shortly before conception. Before administering a live vaccine, women of childbearing age are advised to undergo a pregnancy test. Pregnancy should be avoided for 28 days after administration of a live vaccine and for as long as 3 months after administration of the varicella vaccine. Nevertheless, no significant adverse outcomes have been reported when pregnancy occurred before the recommended interval had elapsed.
Women planning to become pregnant should undergo serological testing to determine immunity to measles, mumps, and rubella. Women without immunity should be vaccinated before becoming pregnant because infection during pregnancy may impair fetal development. Once IgG-class antibodies against rubella have been detected, repeat serological testing before subsequent pregnancies is not necessary. Women who received 1 or 2 doses of the measles, mumps, and rubella vaccine during childhood but whose serological IgG markers are insufficient are advised to receive a booster dose of the measles, mumps, and rubella vaccine. Further serological testing to confirm immunity to rubella is not required.
Varicella zoster infection during pregnancy can cause not only severe maternal disease but also congenital varicella syndrome in the fetus (limb hypoplasia, microcephaly, skin scarring, visual defects) and Varicella zoster infection in the newborn. If a woman has been vaccinated or if her medical records contain a physician-confirmed history of varicella infection or herpes zoster, immunity to varicella may be presumed, but it can only be confirmed by serological testing. Women who do not plan to become pregnant for at least 8 weeks may be vaccinated against varicella. Two doses of the vaccine are administered, with the second dose given 4–8 weeks after the first.
Vaccination During Pregnancy
There is currently no approved preventive vaccination schedule specifically for pregnant women in Lithuania. However, the general practitioner caring for a pregnant woman should assess her vaccination history and, when necessary, recommend the appropriate vaccines. During pregnancy, vaccination with an inactivated influenza vaccine and a tetanus and diphtheria toxoid and acellular pertussis vaccine is recommended.
Influenza Vaccination During Pregnancy
Influenza is the most common viral infection among pregnant women, and the risk of influenza complications and the rate of hospitalization due to influenza infection are considerably higher in pregnant women than in non-pregnant women of the same age. The influenza virus does not enter the bloodstream or cross the placenta; however, cytokine release and fever may result in fetal developmental abnormalities and increase the risk of pregnancy loss or preterm birth.
Inactivated split-virus or subunit influenza vaccines do not contain influenza virus and therefore cannot cause the disease in a vaccinated pregnant woman. Influenza vaccination during pregnancy protects not only the woman against severe disease or its complications but also the newborn during the first months of life. Influenza vaccination can be administered not only during pregnancy but also after delivery and while breastfeeding. Pregnant women are considered an influenza risk group and can therefore be vaccinated free of charge during any trimester of pregnancy.
Vaccination Against Tetanus, Diphtheria, and Pertussis During Pregnancy
Several thousand cases of neonatal tetanus are registered worldwide each year, mainly in Africa and Asia. Neonatal tetanus is very rare in Europe. The tetanus and diphtheria toxoid vaccine intended for adults contains a lower amount of diphtheria toxoid than the vaccine intended for children. The primary purpose of immunizing pregnant women with this vaccine is to prevent neonatal tetanus. Ideally, a woman should be vaccinated before pregnancy, but the vaccine is also safe for pregnant women.
The tetanus, diphtheria, and pertussis vaccine intended for adults contains a lower amount of pertussis antigens than the DTaP vaccine intended for children. In the event of an injury or burn, particularly a deep puncture wound contaminated with soil, tetanus vaccination of the pregnant woman is necessary as part of wound management and can be performed at any stage of pregnancy.
Pregnant women do not develop pertussis more frequently or more severely, but because of immature cellular immunity, pertussis is most dangerous for unvaccinated newborns. Vaccination against pertussis is recommended between 27 and 38 weeks of pregnancy. Adolescents and other family members living in the household who were last vaccinated more than 10 years ago are also advised to receive pertussis vaccination, thereby creating protection for the newborn (the cocoon strategy) until the infant can be vaccinated according to the childhood vaccination schedule.
Table 1. Vaccines That May Be Administered Before Pregnancy, During Pregnancy, and After Delivery
| Vaccine | Before Pregnancy | During Pregnancy | After Delivery | Vaccine Type |
|---|---|---|---|---|
| Hepatitis A | Yes, if indicated | Yes, if indicated | Yes, if indicated | Inactivated |
| Hepatitis B | Yes, if indicated | Yes, if indicated | Yes, if indicated | Inactivated |
| Human papillomavirus | Yes, if indicated, up to 26 years of age | No, studies are ongoing | Yes, if indicated, up to 26 years of age | Inactivated |
| Influenza | Yes | Yes | Yes | Inactivated |
| Measles, mumps, rubella | Yes, if indicated; avoid pregnancy for 4 weeks | No | Yes, if indicated | Live |
| Meningococcal / pneumococcal: conjugate polysaccharide | If indicated | If indicated | If indicated | Inactivated |
| Tdap | Yes, if indicated | Yes, during each pregnancy, preferably between 27 and 36 weeks of gestation | Yes, immediately after delivery if not previously vaccinated | Toxoid / inactivated |
| Tetanus / diphtheria Td | Yes, if indicated | Yes, if indicated; better than Tdap | Yes, if indicated | Toxoid |
| Varicella | Yes, if indicated; avoid pregnancy for 4 weeks | No | Yes, if indicated; vaccinate immediately after delivery | Live |
Vaccination of Pregnant Women With Other Vaccines
Pneumococcal polysaccharide, Haemophilus influenzae type b (Hib), and meningococcal vaccines are recommended for adult women who are at increased risk of these infections. These include women living in or planning to travel to areas where these pathogens are endemic, those who may be exposed to infection at work, and those with certain medical conditions (e.g., after splenectomy, or with leukemia, HIV, or other diseases). Ideally, vaccination should be performed before pregnancy; however, vaccination during the second and third trimesters is considered safe. The safety of these vaccines in early pregnancy has not been studied, but no adverse reactions associated with vaccination during pregnancy have been documented. In all cases, the risk posed by these diseases and their complications to the pregnant woman and fetus is many times greater than the theoretical risk of possible adverse effects from the vaccines used to prevent them.
Pregnant women may be vaccinated against hepatitis B. Since 1998, newborns in Lithuania have been vaccinated against hepatitis B, and since 2002, 12-year-olds have also been vaccinated. However, most adults living in Lithuania have not been vaccinated against hepatitis B. The hepatitis B vaccine is recombinant and therefore cannot harm the fetus or newborn if the mother is vaccinated during pregnancy. Hepatitis B vaccination may be continued in a woman who becomes pregnant after starting the vaccination series before pregnancy, regardless of the stage of pregnancy. If indicated, pregnant women may also be vaccinated against hepatitis A.
Yellow fever is a viral infection transmitted by tropical mosquitoes. It is prevalent in South America and sub-Saharan Africa and is often fatal. Travel to countries where yellow fever is endemic should be avoided during pregnancy. If travel is unavoidable and the risk of yellow fever virus infection is high, vaccination against yellow fever is recommended. Pregnant women traveling to a yellow fever-endemic country are also advised to avoid contact with mosquitoes that transmit the virus by remaining in urban areas, avoiding going outdoors at dawn and dusk, wearing protective clothing outdoors, and using special repellents on exposed areas of skin.
Studies have shown that this vaccine can be administered during pregnancy. The risk of fetal infection is low. If a woman is vaccinated while already pregnant, termination of pregnancy is not recommended. It is preferable not to administer the yellow fever vaccine to a breastfeeding woman unless the risk is very high.
Summary and Recommendations
Ideally, women should receive the recommended vaccines before becoming pregnant. Women of childbearing age who are planning pregnancy should ensure that they have immunity to measles, rubella, mumps, and varicella and, if not, should be vaccinated before pregnancy because these live attenuated vaccines are contraindicated during pregnancy, while infection in unvaccinated pregnant women may cause pregnancy complications.
Before vaccinating women of childbearing age, it should be confirmed that the woman is not pregnant and does not plan to become pregnant within the next 4 weeks. The woman should be informed about the potential effects and risks of live attenuated vaccines during pregnancy when vaccination is performed during pregnancy or shortly before conception.
Vaccination with live vaccines is not recommended during pregnancy. Pregnancy should be avoided for 28 days after administration of a live vaccine. However, no teratogenic effects on the fetus have been observed when pregnancy occurred immediately after vaccination with live measles, mumps, rubella, varicella, or yellow fever vaccines. Therefore, termination of pregnancy solely because a live vaccine was administered is not justified.
Pregnant women should avoid traveling to areas where there is an increased risk of serious infectious diseases (e.g., countries with a very high risk of yellow fever). They should also ensure that family members are vaccinated according to the national vaccination schedule and follow appropriate hygiene practices.
All pregnant women, regardless of the stage of pregnancy, should receive the inactivated seasonal influenza vaccine before the beginning of the influenza season, funded by the state. Importantly, maternal immunization provides passive immunity to the infant during the first months of life.
Every pregnant woman is recommended to receive the tetanus and diphtheria toxoid and acellular pertussis vaccine (Tdap) between 27 and 36 weeks of pregnancy, even if she has previously had pertussis or has previously been vaccinated against it.
Pregnant women with other medical conditions or those belonging to risk groups for hepatitis A or B virus infection, pneumococcal infection, Haemophilus influenzae type b infection, or meningococcal infection may be vaccinated with inactivated vaccines. If the risk of contracting yellow fever is greater than the potential risk associated with vaccination, consultation with an infectious disease specialist regarding vaccination with the live yellow fever vaccine is necessary. If the risk of infection is low but vaccination is required for entry into another country, a medical exemption document may be issued.
Measles, mumps, rubella, and varicella vaccines should be avoided during pregnancy. Women without immunity may receive these vaccines before pregnancy or after delivery.
Vilija Sniečkuvienė, Department of Obstetrics and Gynecology, Faculty of Medicine, Vilnius University
Agnė Misiūtė, Faculty of Medicine, Vilnius University
Assoc. Prof. Dr. Ligita Jančorienė, Department of Infectious Diseases, Chest Diseases, Dermatovenereology and Allergology, Faculty of Medicine, Vilnius University
GINEKOLOGIJOS AKTUALIJOS, supplement to the journal INTERNISTAS, 2016, No. 1
