Vaccine Hesitancy

The COVID-19 pandemic brought vaccine hesitancy back to the forefront. The first COVID-19 vaccine received Emergency Use Authorization (EUA) from the U.S. Food and Drug Administration (FDA) in December 2020. Since that time, more than 675 million COVID-19 vaccine doses have been administered and approximately 80% of Americans have received at least 1 COVID vaccine dose, but many younger adults and children remain unvaccinated (1). Vaccine hesitancy has increased with the more recent monovalent vaccines now used primarily as boosters after completion of the original vaccine series. As of January 4, 2025, only 11% of children were reported to be up to date with the 2024–2025 COVID-19 vaccine (2).

Serious adverse events associated with COVID-19 vaccination can occur but are extremely rare. For example, the mRNA vaccines, SARS-CoV-2 virus (COVID-19) mRNA vaccine produced by Pfizer-BioNTech and SARS-CoV-2 virus (COVID-19) mRNA vaccine produced by Moderna, have been associated with Serious adverse events associated with COVID-19 vaccination can occur but are extremely rare. For example, the mRNA vaccines, SARS-CoV-2 virus (COVID-19) mRNA vaccine produced by Pfizer-BioNTech and SARS-CoV-2 virus (COVID-19) mRNA vaccine produced by Moderna, have been associated withmyocarditis and pericarditis. Although serious, these events are extremely rare compared to COVID-19 infection and its complications (3). Similar to other vaccine-preventable diseases, hospitalizations and emergency department visits resulting from COVID-19 infection are more common among unvaccinated people (4).

COVID-19 infection can affect children and adolescents and can also cause severe outcomes. Additionally, children and adolescents are susceptible to long COVID (a chronic condition occurring after SARS-CoV-2 infection and present for at least 3 months), and research suggests that people who develop a COVID-19 infection after vaccination note a moderately protective effect of vaccination against long COVID, especially in adolescents, compared to people who are unvaccinated (see CDC: Long COVID Basics) (5).

The Institute of Medicine (IOM) of the United States National Academy of Sciences, the CDC, and the American Academy of Pediatrics (AAP) have found no link between vaccines and autism spectrum disorder (1, 2, 3). 

A concern was raised in 1998 when a report published in The Lancet postulated a link between the measles virus in the MMR vaccine and autism spectrum disorder and received significant media attention worldwide; consequently, many parents began to doubt the safety of the MMR vaccine. The report was retracted in 2010 (4), and the first author was removed from the United Kingdom medical register, with a statement regarding intentional falsification of research.

The initial publication reported that 8 of 12 children who received the MMR vaccine developed autism spectrum disorder and that measles virus was found more often in intestinal biopsies of children with autism versus those without autism; as noted, this report was retracted. Subsequent data have not supported an association between the MMR vaccine and autism spectrum disorder.

Numerous other researchers studied the possible connection between the MMR vaccine and autism spectrum disorder. In a review of 13 large epidemiologic studies, all included studies failed to support an association between MMR vaccine and autism spectrum disorder (5). Many of these studies showed that national trends of MMR vaccination were not directly associated with national trends in the diagnosis of autism spectrum disorder. For example, in the United Kingdom between 1988 and 1999, the rate of MMR vaccination did not change, but the rate of autism spectrum disorder increased.

Other studies compared the risk of autism spectrum disorder in individual children who did or did not receive the MMR vaccine. In the largest and most compelling of these studies, 537,303 Danish children born between 1991 and 1998 were assessed and 82% of whom had received the MMR vaccine (6). After controlling for possible confounders, they found no difference in the relative risk of autism spectrum disorder in vaccinated and unvaccinated children. Overall incidence of autism spectrum disorder was 608 of 440,655 (0.138%) in the vaccinated group and 130 of 96,648 (0.135%) in the unvaccinated group. A follow-up study involving all children born in Denmark between 1999 and 2010, totaling 657,461 participants, concluded that the MMR vaccine does not cause autism spectrum disorder (hazard ratio 0.93 [95% CI, 0.85 to 1.02]) and does not increase the risk in children with a sibling history of autism spectrum disorder or other autism risk factors (7). Other population-based studies around the world have reached similar conclusions.

A meta-analysis of 10 studies that included over 1.2 million children found no evidence supporting an association between vaccines and their components (including the MMR vaccine and thimerosal) and the development of autism or autism spectrum disorder (8). The measles virus was not detected more often in the children with autism spectrum disorder than in those without.

Despite the overwhelming evidence to support the safety of the MMR vaccines, and the discrediting of the intentionally falsified research, many parents remain hesitant to consent to administration of this vaccine. As a result, the United States experienced the largest number of measles cases in 2019 since 1992. According to the Centers for Disease Control and Prevention (CDC), most infected people were not vaccinated (9).

Thimerosal is a mercury compound previously used as a preservative in many multidose vaccine vials; preservatives are not needed in single-dose vials and cannot be used in live-virus vaccines. Thimerosal is metabolized to ethylmercury, which is eliminated through the gastrointestinal tract quickly from the body. Because environmental methylmercury (which is a different compound that is not eliminated from the body quickly) is toxic to humans, there was concern that the very small amounts of thimerosal used in vaccines might cause neurologic problems, particularly autism spectrum disorder, in children. Because of these theoretical concerns, even though no studies had shown evidence of harm, thimerosal was removed from routine childhood vaccines in the United States, Europe, and several other countries by 2001. However, in these countries, small amounts of thimerosal continue to be used in certain influenza vaccines and in several other vaccines intended for use in adults. For information about vaccines that contain low levels of thimerosal in vaccines, see the FDA: Thimerosal and Vaccines. Thimerosal is also used in many vaccines used in low-resource countries; the World Health Organization (WHO) has not recommended its removal because there is no clinical evidence of toxicity.

Despite the removal of thimerosal, rates of autism spectrum disorder have continued to increase, strongly suggesting that thimerosal in vaccines does not cause autism spectrum disorder. Additionally, 2 separate Vaccine Safety Datalink studies have concluded that there is no association between thimerosal and autism spectrum disorder. In the first study, a cohort study of 124,170 children from 3 managed care organizations (MCOs), no association was found between thimerosal and autism spectrum disorder or other developmental conditions, although inconsistent associations (ie, seen in one MCO but not another) were seen between thimerosal and certain language disorders (1). In the second study, a case-control study of 1000 children (256 with autism spectrum disorder and 752 matched controls without autism spectrum disorder), no association was found between exposure to thimerosal and autism spectrum disorder (2). A systematic review of 12 studies concluded that the preponderance of evidence did not support an association between thimerosal-containing vaccines and autism spectrum disorder (3).

Health care professionals who work with parents who are still concerned about thimerosal in the influenza vaccine may use single-dose vials of injectable vaccine or the live-attenuated nasal spray vaccine, neither of which contains thimerosal.

Concerns regarding the concurrent administration of multiple vaccines in children have prompted significant debate among the public. A nationally representative survey done in the late 1990s revealed that 23% of all parents felt that their children receive more vaccines than they should (1). Since then, additional vaccines have been added to the immunization schedule so that by age 6, children are recommended to receive multiple doses of vaccines for 10 or more infections (see CDC: Child and Adolescent Immunization Schedule by Age). To minimize the number of injections and visits, clinicians give many vaccines as combination products (eg, diphtheria-tetanus-pertussis, measles-mumps-rubella). However, some parents have become concerned that the children's (particularly infants') immune system cannot handle multiple simultaneously presented antigens. This concern has caused some parents to request alternative immunization schedules that delay and sometimes completely exclude certain vaccines. A 2011 nationally representative survey found that 13% of parents use such a schedule (2).

The use of alternative schedules is risky and scientifically unfounded. The recommended schedule is designed to protect children against diseases when they are most susceptible. Delaying vaccination increases the amount of time children are at risk of acquiring these diseases. In addition, although parents may plan to only delay vaccination, the increased number of visits needed for alternative schedules increases the difficulty of adherence and thus the risk that children ultimately may not receive a full series of vaccines. Regarding the immunologic challenges, parents should be informed that the amount and number of antigens contained in vaccines is miniscule compared with that encountered in everyday life. Even at birth, an infant's immune system is prepared to respond to the hundreds of antigens the infant encounters during delivery and through interactions with the (unsterile) mother. A typical infection with a single organism stimulates an immune response to multiple antigens of that organism (perhaps 4 to 10 in a typical upper respiratory infection). Furthermore, because current vaccines contain fewer antigens overall (ie, because key antigens have been better identified and purified), children are now exposed to fewer vaccine antigens than they were for most of the 20th century. Using data from the Vaccine Safety Datalink, one study compared neurodevelopmental outcomes in a group of children who received all vaccines according to the recommended schedule with a group of children who did not (3). The children in the delayed group did not do better on any of the 42 outcomes tested. These results may reassure parents who are concerned that children receive too many vaccines too soon.

In summary, alternative vaccine schedules are not evidence-based and put children at increased risk of infectious diseases. More importantly, they offer no advantage. Adhering to the recommended vaccination schedule is still currently the best practice in ensuring immunity to vaccine-preventable diseases in children.