Vaccines

Vaccinations during pregnancy have this goal, and vaccinations designed to be administered during pregnancy specifically to protect the infant (rather than the mother) are in development (i.e. RSV).

Vaccinating the mother during pregnancy is a perfect mechanism to not only protect the mother (i.e. influenza), but to provide a baby with antibodies prior to birth.  When the mother is vaccinated, her antibodies safely transfer through the placenta. 

Antibodies from vaccinations during pregnancy are estimated to provide protection to an infant until at least six months old, the time in which the first (post-delivery) vaccinations begin.

Women are often excluded from clinical trials which are required to “officially” obtain approvals – however, safety data has accumulated for decades.

It was not until 2015 in which the U.S. Food and Drug Administration (FDA) convened the Vaccines and Related Biological Products Advisory Committee to discuss clinical trial considerations for vaccines for use during pregnancy (the Committee discusses vaccines for all populations).

Note: According to meeting notes posted to the FDA website, the last vaccine discussed specifically for pregnancy was Group B Strep in May 2018 (as of September 2020).

Vaccines that contain live viruses are not recommended for pregnant women and are routinely avoided; however, to date, any potential harm from these vaccinations during pregnancy is still only theoretical.

Live vaccines are considered strong, and in some cases, can induce unwanted effects compared to other types of vaccines. For example, a live attenuated vaccine against rotavirus can cause severe intestinal inflammation.

Live attenuated vaccines include: Measles, Mumps, and Rubella (MMR); Rotavirus; Smallpox; Chickenpox; Yellow Fever

Inactivated or killed vaccines are created by inactivating a pathogen using heat or chemicals. Inactivating processes destroy the pathogen’s ability to replicate; therefore it does not contain any living or infectious particles and thus cannot result in clinical infection (i.e. the inactivated influenza vaccine cannot give someone influenza).

Inactivated vaccines: Influenza; Hepatitis A; Polio; Rabies

Subunit, recombinant, polysaccharide, and conjugate vaccines: Hepatitis B; Human Papillomavirus (HPV); Whooping Cough (part of Tdap and DTap); Pneumococcal Disease; Meningococcal Disease; Shingles (boosters of these vaccines are often required).

Toxoid vaccines: Diphtheria; Tetanus (see Tdap, below).

Pregnancy is considered a risk factor for developing severe influenza infection, reported by different countries all over the world. Pregnancy may possibly be a stronger risk factor than obesity, diabetes, and cardiac failure.

Influenza in infants under six months old can be devastating; this age group is at risk for higher hospitalization rates than children six to twelve months of age during flu seasons.

More than 40 years of research, safety data, and hundreds of thousands of vaccinations have demonstrated the safety and effectiveness of the influenza vaccine during pregnancy – for both pregnant women and their newborns.

Specifically, there is a strong lack of association between autism, malignancy, birth defects, or fetal death. Additionally, some studies found better pregnancy outcomes in those who were vaccinated when compared to women who were not vaccinated.

Further, during the 2009–2010 influenza A (H1N1) vaccination program, clinical trials were conducted and several monitoring systems were established; these evaluations did not identify any safety concerns in vaccinated pregnant women or their infants.

Data have shown the vaccine prevents neonatal morbidity and hospitalization from influenza virus infection in the first six months of life. Numerous studies have also found neonatal antibodies at approximately the same level as levels in the mother’s blood.

Although there is overall less data during the first trimester, it appears the stage of gestation does not seem to influence the response rate; effectiveness in the first trimester is similar to second and third trimester vaccination.

Further, while a review of articles between 1964 and 2013 indicated the vaccine may only provide moderate protection in some cases, the same study pointed out that even if influenza vaccination provides sub-optimal protection in pregnant women, its potential to provide protection to young infants is enough justification to recommend the vaccine.

However, it also recommended that pregnant women with certain medical conditions that increase their risk for complications should be vaccinated before the influenza season regardless of trimester.

Diphtheria: is an infection of the nasal, pharyngeal, laryngeal, or other mucous membranes that can cause nerve and heart muscle inflammation, platelet deficiency, and ascending paralysis.

Tetanus: causes production of a neurotoxin that is often fatal; symptoms include painful muscle contractions of the jaw and neck; neonatal tetanus may occur in newborns who have low levels of anti-tetanus antibody due to a lack of passively transferred antibodies from the mother.

Pertussis: also known as whooping cough, is a highly contagious respiratory infection most severe in infants or in individuals who have never been immunized against the disease; the infection can last 6 to 10 weeks and cause a “whooping” sound when an infected individual breathes in.

Since the 1980s, pertussis has been on the rise in the U.S. In 2012, CDC saw the most cases in 60 years; of the 48,277 reported cases, 2,269 of those cases were in infants younger than three months old and 15 infants died.

It is unclear if the resurgence may be due to a mutation in the bacteria, improved diagnostic testing and increased reporting, or rapid waning of vaccination immunity (antibodies).

Most pertussis deaths are infants who are too young to be protected by the childhood pertussis vaccine. Infants do not begin their own vaccine series against pertussis until approximately two months of age. This leaves a window of significant vulnerability for newborns, many of whom may contract the disease from close family in the first few weeks of life.  It is estimated that 47% to 60% of infected infants are exposed to the disease from their parents.

In 2006, the Advisory Committee on Immunization Practices (ACIP) of the CDC recommended a practice known as “cocooning” and this method has been adopted by various additional organizations. Cocooning involves administering the Tdap to previously unvaccinated family members and those expected to be in close contact with the newborn at least two weeks before the baby is born.

Due to the 2012 outbreak, CDC and many other organizations recommend all pregnant women receive the Tdap vaccine, regardless of their last booster, during their third trimester of each pregnancy (ideally between weeks 27 and 36) for the most optimal protection of the newborn.

Further, if a woman has not been vaccinated with Tdap recently, or did not receive one during pregnancy, she should receive one in the immediate postpartum, to prevent her from passing pertussis to her infant.

However, if a pregnant woman requires the Tdap vaccine due to the prevention of a wound infection (tetanus) during pregnancy, she should be given the vaccination regardless of gestational age and should not receive a second vaccination during the third trimester.

Although Tdap is a combination vaccine, it is has been estimated the tetanus toxoid vaccine alone was administered to 100 million pregnant women around the world in 2011. The safety of widespread tetanus toxoid vaccine use over the past 40 years, and the substantial decrease in neonatal tetanus supports the safety and effectiveness of the vaccine.

A study published in August 2021 assessed the effectiveness of the vaccine in producing antibodies. Recently vaccinated women had significantly higher Pertussis antibody titers (even 12–15 times as high) compared to those vaccinated more than 5 years before or never vaccinated at all.

A study published in April 2021 assessed the relationship between maternal Tdap vaccination and obstetric and perinatal outcomes in Ontario. Of 615,213 infants (live births and stillbirths), 11,519 were exposed to Tdap vaccination in utero. Study results indicated maternal Tdap vaccination is not associated with adverse outcomes in mothers or infants.

A clinical trial of the Tdap vaccine for mothers and infants was completed in 2014. The preliminary safety assessment did not find an increased risk of adverse events among women who received Tdap vaccine at 30 to 32 weeks’ gestation or their infants.  Further, maternal immunization resulted in high concentrations of pertussis antibodies in the infants during the first two months of life.

A study published in April 2021 described the pertussis morbidity and mortality trends in infants less than or equal to 2 and 12 months of age, before and after maternal Tdap immunization implementation in Mexico (that started in 2013). After maternal immunization was implemented, there was a decreasing trend in incidence, hospitalization and death due to pertussis in infants 0-2 months old.

Breast milk antibodies: Clinical trial results published in September 2021 found that maternal Tdap vaccination induces high antibody levels in breast milk after both term and preterm delivery and that these antibodies remain abundantly present throughout lactation, possibly offering additional mucosal protection during the most vulnerable period in early life.

It is recommended that all pregnant women be screened for hepatitis B during standard early prenatal care; although most newborn infections occur during delivery, transmission during pregnancy has occurred, especially when a pregnant woman contracts a primary (first) infection late in pregnancy.

Pregnant women may be considered at risk for infection if they are having sex with a man who has sex with men, have multiple sexual partners, are using or abusing intravenous drugs, have occupational exposure, or are a household contact of an infected person (through any body fluid). A series of three vaccines is considered highly effective, providing an indefinite protective antibody response in greater than 90% of those vaccinated.

Women who believe they may be at risk for Hepatitis B infection during pregnancy should talk to their HCP.

While there is insufficient safety data regarding a Hepatitis A vaccine during pregnancy, it is an inactivated vaccine and is not expected to cause harm or an infection. It is recommended pregnant women receive the vaccination if they are at risk of contracting Hepatitis A infection.

Women may be at increased risk if they have direct contact with someone who has Hepatitis A, they travel to a country where the infection is common, they use intravenous drugs, or have a clotting disorder.

Women who believe they may be at risk for Hepatitis A infection during pregnancy should talk to their HCP.

The ACIP currently recommends that women at high-risk be vaccinated before, but not during, pregnancy. The safety of the pneumococcal vaccine during pregnancy has not been evaluated, although no adverse effects have been reported in newborns whose mothers were inadvertently vaccinated.

According to the CDC, risk factors for pneumococcal infection include decreased immune function from disease or drugs, abnormal function of the spleen, chronic heart, lung (including asthma), liver, or renal disease, cigarette smoking, cerebrospinal fluid leak, or a cochlear implant (due to increased risk of meningitis).

Measles: a highly contagious disease that can cause complications such as ear infections, diarrhea, pneumonia, and encephalitis; measles is most often recognized by its wide-spread rash all over the body; measles can be passed to the baby during pregnancy, even with maternal asymptomatic infection.

Mumps: a contagious disease caused by a virus; symptoms include fever, headache, muscle aches, tiredness, and loss of appetite; most commonly recognized by swelling of the salivary glands, causing puffy cheeks and a tender, swollen jaw.

Rubella: contagious viral infection that can cause rash and fever in children and adults, but can be devastating during pregnancy, leading to congenital rubella syndrome; rubella during pregnancy can cause miscarriage, stillbirth, serious birth defects, or life-long illness in the child; ideally, HCPs test for a woman’s antibody levels (titer) at a preconception appointment.

However, if a woman was inadvertently vaccinated during pregnancy, estimated risks to the fetus are considered very small.

Travelers to rural parts of Asia have an increased risk of acquiring JE infection, which is estimated at approximately 1 in 5,000 per month. In short-term travelers to urban areas, risk of infection is estimated at less than one per million.

There are no adequate studies of the vaccine during pregnancy, and the vaccine is not recommended unless the woman is considered at high-risk for infection. High-risk includes longer-duration travel to endemic areas, in which the risk of infection may outweigh the possible risks of vaccination.

There is no safety-related information regarding the yellow fever vaccine during pregnancy. As the vaccine is live attenuated, it is not recommended for pregnant women unless there is an epidemic or the woman is travelling to a high-risk area. At least one study documented inadvertent vaccination of pregnant women and demonstrated no association with toxic effects, miscarriage, or preterm birth.

Most cases of typhoid fever occur in travelers who recently have returned from high-risk areas, such as South America, India, and western Africa, or moderate-risk areas, such as Mexico, Haiti, northern Africa, and Iran.

The two types of typhoid vaccination in use today are a live attenuated oral vaccine and a parenteral polysaccharide vaccine. Both forms require that immunization be completed at least two weeks before exposure. Unfortunately, there are no data supporting the efficacy and safety of either vaccine in pregnancy, and CDC has made no specific recommendations regarding these vaccines during pregnancy.

While research is ongoing regarding a vaccine for infants and young children, this research also includes a vaccine that could be administered to pregnant women that would pass antibodies to the infant even before birth (read Respiratory Infections for more information regarding RSV infection during pregnancy). As of July 2021, numerous clinical trials are underway.

One profile of the the RSV F recombinant nanoparticle vaccine was published in May 2021. The vaccine was safe and well tolerated in pregnant women and the results suggested potential benefits, but it did not meet the success criteria for efficacy against RSV-associated, respiratory tract infection in infants up to 90 days of life. Therefore, research remains ongoing.

RSV in infants cases started climbing around the U.S. in July 2021, spurring at least one state (Texas) to recruit pregnant women for an RSV vaccine trial.

A GBS vaccine has been theorized to potentially be a more effective and reliable way to prevent both early- and late-onset disease in newborns/infants. As of June 2020, at least one vaccine was currently in phase II, and one vaccine had completed phase II with promising results.