Overview

Flu, or influenza, is a contagious disease caused by the influenza virus. In most healthy adults, flu symptoms are typically mild and resolve within about a week. However, during pregnancy, the body’s heightened inflammatory response can increase the risk of complications from the flu. To reduce these risks and provide passive immunity to babies, healthcare professionals recommend the flu vaccine for pregnant women. Deciding whether to get vaccinated during pregnancy can be challenging, as it involves weighing the potential risks and benefits. Additionally, you have choices regarding the type of flu vaccine and the timing of administration. This episode reviews the research and considerations for making an informed decision about the flu vaccine during pregnancy.

This episode is up to date for the 2023-24 flu season.

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What is a Vaccine?

Vaccines have been around since the 1790s, beginning with the smallpox vaccine. Let’s first cover some basics to better understand how vaccines work and their risks and benefits. Traditionally, vaccines use a weakened or killed version of a disease-causing microorganism or parts of it, like its toxins or surface proteins. When given, typically through an injection, vaccines trigger your immune system to produce antibodies against the disease without causing illness. Essentially, the vaccine teaches your body to recognize and fight the disease if you encounter it in the future. In some cases, immunity lasts a lifetime; in others, booster shots may be necessary to maintain protection.

Types of Vaccines

Different types of vaccines use various methods to stimulate immunity. Inactivated vaccines use micro-organisms that have been killed, often through heat, radiation, or chemicals. The flu vaccine is an inactivated vaccine.

There are also attenuated vaccines that contain live but weakened micro-organisms. These are strong enough to trigger an immune response but not enough to cause illness. A flu vaccine is available as a live attenuated nasal spray. However, this is not recommended during pregnancy. Toxoid vaccines use inactivated toxins from bacteria, such as those in the Tdap vaccine, which protects against tetanus and diphtheria. Subunit vaccines use specific proteins or pieces of the pathogen to trigger an immune response. This method is used for certain vaccines like the HPV vaccine.

mRNA vaccines, a newer technology used for COVID-19 vaccines, work differently. Instead of using part of the virus or bacteria, these vaccines instruct your cells to make a protein that triggers an immune response. This teaches your immune system to recognize and fight the virus if you are exposed to it in the future.

Vaccine Ingredients

Vaccines often contain additional ingredients to ensure safety and effectiveness. Adjuvants like aluminum salts help boost the immune response to the vaccine. Stabilizers are used to maintain the vaccine’s potency during storage and transport. Preservatives are used in multidose vials to prevent contamination. Thimerosal, a mercury-containing preservative, has been used in some multidose vaccines but is not present in most other vaccines today due to concerns. Lipid nanoparticles (tiny fat particles) are included in mRNA vaccines to protect the fragile mRNA and help it enter your cells. Other vaccines may contain trace amounts of antibiotics to prevent bacterial growth, formaldehyde (used to inactivate toxins or kill viruses and bacteria during the production process), and in some cases, egg proteins, if the virus is grown in eggs, as is the case for certain flu vaccines.

Immunity

Different forms of immunity can result from vaccination. Individual immunity occurs when a single person develops immunity after receiving a vaccine. Passive immunity happens when a pregnant mother passes antibodies to her baby through the placenta or later through breast milk, providing the baby with temporary protection. This is a significant driver for vaccines recommended during pregnancy. Herd immunity occurs when a large portion of the population is vaccinated, reducing the spread of disease. Herd immunity is crucial for protecting individuals who cannot get vaccinated, such as those with compromised immune systems, allergies to vaccine ingredients, or babies too young to be vaccinated.

Evaluating Vaccines

I follow a systematic approach and conduct thorough research when evaluating any vaccine or medical intervention. I ask several key questions:

• What are the risks of the illness the vaccine is targeting?
• What is the history of the vaccine?
• What ingredients are in the vaccine?
• How effective is it?
• What are the risks and benefits?

In addition to these general questions, I consider personal factors like my current health status, the likelihood of exposure, where I live, places I may travel to, and the time of year. Answering these questions requires a significant amount of research and critical thinking.

The Controversy Surrounding Vaccines

Vaccines are a complex and often controversial topic. Some professionals dedicate their careers to researching and studying vaccine safety and efficacy. This makes researching vaccines challenging, as it’s easy to come across information that appears unbiased but may ultimately push a pro- or anti-vaccine agenda. This episode aims to provide an objective overview of the data so you can make an informed decision. If you have additional questions or concerns, discuss them with your doctor or midwife.

The Role of the Centers for Disease Control and the World Health Organization 

In recent years, there have been growing questions about the reliability of information from organizations like the CDC and WHO and the potential influence of pharmaceutical companies on these organizations. However, it’s important to note that the CDC and WHO maintain some of the most extensive centralized databases for disease statistics.

While these organizations focus on protecting public health on a national and global scale, their guidelines often inform recommendations by bodies like the American College of Obstetricians and Gynecologists (ACOG), which, in turn, influence your healthcare provider’s advice. Ultimately, your primary concern is the safety and efficacy of a vaccine for you and your baby. Understanding the information that informs your doctor’s or midwife’s recommendations will equip you to have an educated conversation with them and help you make the best decision for your pregnancy.

What is the flu?  

Flu is short for influenza. This is an infectious disease caused by the influenza virus. Like any virus, the flu replicates in living cells. The flu is highly contagious because it can be airborne and on surfaces. It becomes airborne when someone who is infected coughs or sneezes. This releases half a million particles into the air. You can also contract the flu virus by touching a contaminated surface and then touching your mouth, nose, or eyes. The flu virus can live 1-2 days on hard, nonporous surfaces, like a doorknob, 15 minutes on dry paper tissues, like a dollar bill, and only about 5 minutes on the skin. Please wash your hands often and try to avoid touching your face. 

The flu’s symptoms include fever, runny nose, sore throat, muscle pains, headache, coughing, and fatigue. The sudden onset of symptoms and exhaustion with the flu can help you distinguish it from a cold. Symptoms generally appear two days after you are infected and last about a week. A lingering cough may last longer. Complications of the flu can be pneumonia and sinus infections. There are a couple of prescription antiviral drugs to treat the flu.

The flu usually isn’t a big deal if you are a generally healthy adult. You are much more likely to have complications if you are very young, elderly, or have a weakened immune system. Pregnancy does increase your risk for complications with the flu.

The Flu and Your Baby

Part of the push for pregnant mothers to get the vaccine is to transfer immunity to protect their babies. The CDC recommends that babies older than six months get a flu shot every year. According to the CDC, between 6,000 and 27,000 children younger than five years are hospitalized annually because of influenza complications. Since the 2004-2005 flu season, flu-related deaths in children reported to CDC during regular flu seasons have ranged from a low of 37 to a high of 199 deaths.

How the Flu Affects You During Pregnancy  

Influenza causes your body to release large amounts of cytokines and chemokines. These are cells produced by your immune system. This causes inflammation, which we see as redness, swelling, pain, or heat. Think about sore muscles and fever when you have the flu. The positive side of inflammation is that it creates an immune response to fight off whatever is causing the inflammation. 

A Stanford University study found that pregnant women have an unusually strong immune response to influenza. This may explain why pregnant women get sicker from the flu than healthy adults. Physiological changes such as immunological changes, increased cardiac output, oxygen consumption, and lung tidal volume might increase the susceptibility to influenza complications if infection occurs during pregnancy. 

Types of Flu  

Three types of flu affect humans: A, B, and C. A is the most serious in humans and is commonly carried by birds. All the major flu pandemics documented in our history were type A. Type B is less common and mutates 2-3 times slower. The only animals it affects are seals and ferrets, and it almost exclusively affects humans. We rarely have epidemics of type B. Type C affects humans, dogs, and pigs, is the least common, and tends to be the mildest. Vaccines usually include type A and B and do not have type C.  

Within the different types of flu, there are subtypes. You will see the letter H followed by a number and N followed by a number. These Hs and N’s are protein spikes on the virus’s surface that help the virus invade cells. The H stands for hemagglutinin, of which there are 16 types, and the N stands for neuraminidase, of which there are nine .

How the Flu Virus Mutates  

An excellent example of how these viruses mutate I’m borrowing from an NPR article that explains this in straightforward terms. Imagine a bird gets infected with two viruses: H1N1 and H2N2. When the two viruses reproduce inside the bird’s cells, H1N1 can grab accessories from H2N2. This creates a new strain that looks like H2N2 but can now infect people (because it started as just H1N1). This article specifically talks about the 2009 flu. The virus had some segments from H3N2 circulating in humans from the 1968 pandemic. It had genes from birds, an H1 from pigs, and an N1 from a completely different virus. All of these are then mixed in pigs. You can see this gets messy and complicated very quickly.  

The Flu Vaccine  

The influenza virus is a very rapidly evolving virus. For this reason, we cannot make a one-time vaccine. Every year, the flu vaccine is formulated for 3 or 4 viruses. Vaccine virus selection has been conducted by the WHO Global Influenza Surveillance and Response System (GISRS) since 1973. The World Health Organization predicts which flu strains will be the most common the following year. Once the WHO chooses specific strains, it takes six months to produce the vaccine.

Flu Season  

There are two vaccines each year because of two flu seasons—one during winter in the upper hemisphere and one during winter in the lower hemisphere. Flu season tends to be during winter, partly due to the lack of humidity and low UV light. During the winter, more people are indoors, so the flu virus spreads more easily. Plus, the virus survives longer on surfaces at colder temperatures. There is a theory that lower vitamin D levels help spread this virus during winter. I’m not going to examine this in-depth here, and if you want to dig deeper into vitamin D, you can listen to this episode.

How the Flu Vaccine Works  

Historically, vaccines all work on a similar principle. They introduce some part of a bacteria, virus, or pathogen into your body to trigger an immune response. Your body produces antigens to fight off bacteria, viruses, or pathogens and then recognizes and fights them off in the future. Ultimately, the goal is to become immune, which is why we also call vaccines immunizations. 

Once you get the flu vaccine, it takes your body about two weeks to develop antibodies. When you are pregnant, you can pass antibodies to your baby through the placenta, creating passive immunity for your baby. Remember that your baby cannot get a flu vaccine until six months old. This is one of the reasons this vaccine is recommended during pregnancy.

After your baby is born, you continue to pass antibodies to them through your breast milk. I cannot stress enough the importance of breastfeeding, especially during the first few months of your baby’s life. Even if your baby is getting formula and every meal isn’t breast milk, those antibodies you pass when you breastfeed are amazing. Breastfeeding will significantly improve your newborn’s immune system and help to keep them healthier.

When to Get the Vaccine?   

The Centers for Disease Control states you can get a flu shot during any trimester. One study showed that the influenza vaccination at any time during the second and third trimester of pregnancy, but at least 15 days before delivery, creates passive immunity. Most vaccine research has not been done on women in the first trimester because this is a critical development period and the period in which miscarriage is the highest. For these reasons, some expecting mothers and care providers may avoid a flu shot during the first trimester. Talk to your doctor or midwife about the timing of a flu vaccine.

Combining Flu and Other Vaccines  

An additional consideration regarding the timing of the flu vaccine is whether to get it simultaneously with other vaccines. According to the American College of Obstetricians and Gynecologists, if the timing of the influenza vaccine aligns with other inactivated or non–virus-containing vaccines recommended in pregnancy, such as the Tdap, RSV, or COVID-19 vaccine, it is safe and effective to administer these vaccines during the same visit.

In one of the clinical trials disclosed in the Adacel Tdap vaccine package insert, they found that when the Adacel vaccine was administered simultaneously as a trivalent inactivated influenza vaccine, a lower antibody response was observed for pertactin antigen compared to when the Adacel vaccine was administered alone. The pertactin antigen helps you develop immunity to pertussis. If you plan to get Tdap and flu shots during pregnancy, discuss the timing with your doctor or midwife. However, they will likely align with ACOG in recommending you get them during the same visit.

Types of Flu Vaccines 

Some vaccines, like the Tdap, are relatively easy to compare manufacturers because there are only two. This is much more challenging with the flu because nine vaccines are available for the 2023-24 flu season. You can compare the vaccine options on the CDC website, and we will provide more details about comparing your options.

Ingredients in Flu Vaccines   

Flu vaccine ingredients vary depending on the type and brand. They can contain trace amounts of eggs. Some vaccines contain formaldehyde, which is used in growth mediums and processing or added to the final product. The amount of formaldehyde is much less than is naturally contained in your blood. Vaccines could also contain gelatin from animal collagen, making it stable during storage and shipping.

Egg Based Vaccines  

Egg-based vaccines have been around for 70 years. To make these, a lab partner of the WHO (or the CDC in the U.S.) provides candidate vaccine viruses grown in eggs. The viruses go to private companies that inject them into fertilized hens’ eggs so they can multiply. The liquid is taken from the eggs containing the virus and then killed or inactivated. There is a concern about this type of vaccine if you have an egg allergy. The final vaccine has such trace amounts that some people with an allergy don’t have any trouble. There are other options, and if you have an egg allergy, please bring it up with your care provider.

Cell-Based Vaccines  

Cell-based vaccines were approved in 2012. It started in eggs and is now entirely egg-free but grown in animal cells. Cell-based vaccines use Madin Darby Canine Kidney (MDCK-kidney cells from dogs). The benefit of cell-based vaccines is that manufacturers have more control over mutations and, hopefully, a more effective vaccine. Cell-based vaccines are also not dependent on egg supply. Manufacturers can produce cell-based vaccines faster in an epidemic scenario because they do not rely on a large supply of eggs. Hundreds of thousands of eggs are used each year in flu vaccine production.

Recombinant Vaccines  

Recombinant flu vaccines were approved in 2013. These are made using insect cells and are 100% egg-free. The product contains 45 micrograms (mcg) of hemagglutinin for each of the targeted flu strains, three times what most other flu vaccines contain. The only recombinant vaccine approved for the 2023-24 season is Flublok Quadrivalent, made by Sanofi Pasteur. 

If you are vegan, it is complicated. There is no vegan flu shot, which could be a consideration if you are uncomfortable with animal-derived ingredients.

Mercury in Flu Vaccines (Single vs. Multi Dose)

A single-dose vaccine comes in a vial with enough for one dose for one person, while a multidose vial contains multiple doses for multiple people. Of course, each vaccination uses a new sterile needle, but multidose vaccines require an additional preservative to prevent bacteria and fungi from growing.

Thimerosal (mercury) is added to multidose vaccine vials to prevent bacteria and fungus. Multidose vaccines have about 25 micrograms of thimerosal, and single-dose vaccines are mercury-free. According to the World Health Organization, mercury use in some pharmaceuticals, such as thimerosal (ethyl mercury), used as a preservative in some vaccines, is very small by comparison with other mercury sources. No evidence suggests a possible health hazard resulting from the amounts of thimerosal currently used in human vaccines.

The WHO also states that mercury is a naturally occurring element in air, water, and soil. Mercury exposure – even small amounts – may cause serious health problems and is a threat to the development of the child in utero and early in life. Mercury may have toxic effects on the nervous, digestive, immune systems, lungs, kidneys, skin, and eyes. The WHO considers mercury one of the top ten chemicals of major public health concern.  

  

For the 2023-24 season, only multidose vaccines contain thimerosal. You can request a single-dose vaccine, which does not contain mercury.

Flu Vaccines Available for the 2023-24 Flu Season  

Two of this season’s nine vaccine options are approved for those over 65. One is a nasal spray that uses a live attenuated vaccine. The CDC does not recommend the nasal spray vaccine during pregnancy. If you are pregnant and opt for the flu vaccine, the good news is that you will get an inactivated vaccine, so the virus is not living. The bad news is that you will get an injection since the nasal spray is not an option.

For the 2023-24 flu season, all vaccines are quadrivalent (4-component) and contain two A and two B strains. There are six vaccine options you could receive during pregnancy. Below is the list with a link to all of the filings with the FDA, including the package insert, which contains in-depth information about each vaccine.

1. Afluria Quadrivalent (manufactured by Seqirus) 
2. Fluarix Quadrivalent (manufactured by GlaxoSmithKline) 
3. FluLaval Quadrivalent (manufactured by GlaxoSmithKline) 
4. Fluzone Quadrivalent (manufactured by Sanofi Pasteur) 
5. Flucelvax Quadrivalent (manufactured by Seqirus)   
6. Flublok Quadrivalent (manufactured by Sanofi Pasteur)

Requesting a Specific Vaccine

You could easily spend a lot of time comparing these six vaccine options. If you want to avoid mercury, you can request a single-dose vaccine. If you have an egg allergy, you can request a vaccine that is not egg-based. Otherwise, all six options are very similar.

The American College of Obstetricians and Gynecologists’ official statement is that all women who are or will be pregnant during influenza season receive any licensed, recommended, age-appropriate, inactivated influenza vaccine during any trimester as soon as it is available. The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices and ACOG do not preferentially recommend a specific formulation of the influenza vaccine.

Medical offices, pharmacies, and hospitals must order vaccines before flu season. The vaccine choices available to you may be limited by the vaccine carried by your doctor or midwife. If you prefer a specific brand of vaccine, please talk with your doctor or midwife. You can find the brand you want at a pharmacy or other place in your neighborhood for a low cost. 

The Research on the Safety of Vaccines During Pregnancy

Pregnancy adds an additional layer of caution for any intervention. A lot of research is available on the safety and risks of the flu vaccine during pregnancy. Let’s examine some of these studies.

Inflammatory response 

A study shows that the trivalent influenza virus vaccination elicits a measurable inflammatory response among pregnant women. Although only quadrivalent vaccines are available for expectant mothers during the 2023-24 season, research on vaccines from previous years is still applicable. While the strains of the flu change every year, many of the other ingredients do not. Interestingly, the flu or the flu vaccine creates an inflammatory response, and preeclampsia and preterm birth have an inflammatory component. When you are pregnant, you want to limit inflammation when possible. This study noted that an inflammatory response elicited by vaccination is substantially milder and more transient than  infectious illness, arguing for vaccination’s clinical value. However, further research is needed to confirm that the mild inflammatory response elicited by vaccination is benign in pregnancy. 

Some animal studies show that maternal immune activation during pregnancy can harm the brain development of offspring. I want to stay away from linking autism to vaccines. I haven’t seen concrete evidence of a link or a causal relationship. Also, keep in mind that autism is a spectrum disorder. So that tells us that since it is diagnosed on a spectrum, with varying degrees, it is unlikely there is one cause, and more likely, there are many causes. I acknowledge that there are parents who firmly believe their child developed autism following vaccination.

Some animal studies involving rodents and monkeys could raise questions about how a maternal immune response affects a baby in utero. One study on mice shows that maternal immune activation affects the brain development of a fetus. Ultimately, a flu shot creates an immune response, as does the flu. The bottom line is that there is a lot we do not know about immune reactions during pregnancy and how that potentially affects a baby in utero.

The data we have on humans reflects decades of research showing the safety of the flu vaccine during pregnancy. A systematic review examined 40 studies and confirmed the safety of the flu vaccine in pregnancy. They also found evidence to support a protective effect against preterm birth and low birth weight. The researchers looked at specific outcomes, including preterm birth, low birth weight, small for gestational age newborns, congenital abnormalities, spontaneous abortion, and stillbirth.

The vast majority of studies on humans regarding the safety and effectiveness of the flu vaccine are observational studies. These studies only monitor outcomes without mandating any group receive an intervention or placebo. There has been criticism that observational studies overestimate vaccine effectiveness and safety due to the healthy-vaccinee bias. This is the idea that people in better health are more likely to get the flu vaccine. Despite calls for more randomized controlled trials, most research is observational and may be skewed by the healthy-vaccinee bias.

Flu Vaccine and Miscarriage   

There was a study that made headlines about the flu vaccine and miscarriage. I want to go beyond the clickbait headlines and talk about what this study found and what it could mean for you. The study concluded that first-trimester miscarriage was associated with the flu vaccine when the vaccine was given in the preceding 28 days. The association was significant only among women vaccinated in the previous influenza season. This study examined women who received the 2010-2011 season and 2011-2012 vaccines. The researchers noted that this study does not establish a causal relationship between repeated influenza vaccination and miscarriage, but further research is warranted. 

Of course, the headlines linking the flu vaccine and miscarriage make everyone panic. ACOG acknowledged this study and recommends: Pregnant women should be counseled that because of the lack of evidence of biological plausibility, several notable flaws in this study, and the preponderance of other data showing no association of influenza vaccination and miscarriage, the recommendation for flu vaccine given in any trimester has not changed. The influenza vaccine is made the same way each year, with the only difference being the use of different influenza virus strains.

The study doesn’t tell us much other than more research is needed. If you have any concerns over the flu shot or when to get it during your pregnancy, please bring it up with your doctor or midwife. Remember, this is not mandatory. It is entirely your choice whether you opt to have the flu shot. Like any intervention, this should be an informed consent decision.  

Pregnancy Warnings

Some vaccine manufacturers maintain a pregnancy exposure registry that monitors outcomes in pregnant women who have received a vaccine. All six vaccine options available to you have some variation of the disclaimer that there is insufficient data on the vaccine in pregnant women to inform vaccine-associated risks. We know that pregnant women are underrepresented in vaccine trials.

All vaccines performed a reproductive and developmental toxicity study in animals for the current vaccine or a previous version approved for a past flu season. These studies exposed rats or rabbits to the vaccine before and during pregnancy. There were no adverse effects on fertility or development in animal studies. It would be ideal to have studies on humans rather than animals, but the results of these studies are still good news. 

Possible Side Effects of Flu Vaccines   

If side effects occur, they usually begin soon after the shot and generally last for 1-2 days. Rarely can flu shots cause serious problems like severe allergic reactions. The most common side effects experienced by pregnant women are the same as those experienced by other adults. They are generally mild and include:   

• Soreness, redness, or swelling from the shot   
• Fainting   
• Headache   
• Fever   
• Muscle aches   
• Nausea   
• Fatigue 

Efficacy and Effectiveness of Flu Vaccines   

The success of the flu vaccine depends on both efficacy and effectiveness. The CDC measures efficacy with randomized studies where people get either the flu shot or placebo, compared to whether they get the flu. The CDC measures effectiveness by how many people get the flu and visit a doctor. These are not perfect metrics because they do not include people who got the flu but did not visit a doctor or get tested. 

According to the CDC, one study showed getting a flu shot reduced a pregnant woman’s risk of being hospitalized with flu by an average of 40%. This study examined data collected across many hospitals for over six years. Of 19,450 acute respiratory or fever hospitalizations, only 1,030 pregnant mothers were tested for influenza. Of those, 598 tested positive for the flu. 13% of the women who had the flu were vaccinated, and 22% of those who tested negative were immunized. When the researchers adjusted the vaccine effectiveness for the site, season, season timing, and the presence of any high-risk medical condition, they came up with a figure of 40%.

The CDC states that during seasons when flu vaccine viruses are similar to circulating flu viruses, the flu vaccine has been shown to reduce the risk of having to go to the doctor with flu by 40 – 60%. The CDC has tracked effectiveness since 2003 and publishes effectiveness rates for each year. Overall, it ranges from 10-60% depending on the year. The vaccine effectiveness for the 2022-23 flu season was 42%. Vaccines are based on the four influenza viruses predicted to be the most prevalent for the current flu season. If those predictions are accurate, the vaccines are more effective.

Talk to Your Doctor or Midwife  

As with any intervention during pregnancy, you have options. The flu vaccine should come with informed consent. This means you understand the risks and benefits and can opt in or out. If you choose to get a flu vaccine, you have options on the timing or opting for a specific brand or type of vaccine. Discuss any questions or concerns about the flu vaccines with your doctor or midwife.

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