Vaccine Safety: Examine the Evidence

Agency for Healthcare Research and Quality (AHRQ) Publication No. 21-EHC024 (2021)

This 2021 report is an update to a 2014 report from the Agency for Healthcare Research and Quality (AHRQ). The 2021 update found no new evidence of increased risk of rare adverse events (severe allergy, seizures caused by fever and blood clotting issues) following administration of routine recommended childhood vaccinations.

Glanz JM, et al. JAMA. 2018; 319: 906-913

This study looked at 994 children ages 24-47 months who had an emergency department (ED) or inpatient visit. 193 children were seen for an infectious disease for which there is no vaccine. Reserarchers counted how many antigens the children were exposed to through vaccines. They compared the group of 193 children with the remaining 801 children who were seen for a different reason. There was no significant difference in the two groups of children related to their exposure to multiple vaccines through the first 23 months of life and their risk for infections not targeted by vaccines.

Watanabe A, et al. JAMA Pediatr. 2023; 177(4): 384-394

Reviewers looked closely at data from 17 studies involving 10,935,541 vaccinated and 2,635,251 unvaccinated children between 5 and 11 years of age. They concluded that COVID-19 vaccination was associated with lower risks of SARS-CoV-2 infection, symptomatic COVID-19, hospitalization and multisystem inflammatory syndrome in children. The overall frequency of severe adverse events associated with vaccination, including myocarditis, was low.

Mapindra MP, et al. Neonatology. 2024; 121(3): 271-282

This meta-analysis evaluated six randomized clinical trial studies of the maternal RSV vaccine. It concluded that RSV vaccination is safe for mothers and provides effective antibody levels in infants. The vaccine reduces RSV-related severe disease in babies younger than 6 months. The overall reduction of RSV-related lower respiratory tract infections and hospitalizations in the first 6 months of life ranges between 48% and 52%.

Qiu J, et al. Expert Rev Vaccines. 2024 Jan-Dec; 23(1): 69-81

Researchers compiled and analyzed studies with evidence about strategies to prevent infection with the hepatitis B virus using the hepatitis B vaccine. They concluded that universal hepatitis B vaccination can effectively reduce infection with the virus. Researchers also concluded that adjuvants in vaccines and booster vaccination enhance immune protection without significant reactions. After they analyzed the evidence about safety of the hepatitis B vaccine in the studies, they concluded that most people don't experience side effects. They found that if side effects happen (injection-site pain, fatigue and myalgia), they are mild.

Dai Q, et al. Front. Pediatr. 2025; 13. doi: 10.3389/fped.2025.1652946

Researchers analyzed 11 studies involving 147,274 two-year-old children. They found that, compared with placebo, the PCV vaccine lowered the incidence of pneumonia and increased the level of IgG antibodies.

Shi Q, et al. Vaccines (Basel). 2025 Jun 20; 13(7): 666. doi: 10.3390/vaccines13070666

Researchers reviewed 7 randomized controlled trials and 10 case-control studies published between 2014 and 2024. They concluded the trials and studies did not show a significant association between Tdap vaccination during pregnancy and serious adverse events in infants and pregnant women.

Center for Infectious Disease Research and Policy. Vaccine Integrity Project. Hepatitis B

This 2025 report looks at information and recommendations from the past 40 years related to universal hepatitis B vaccination at birth in the United States. Sources of information included epidemiological trends, vaccine coverage, clinical trials, clinical studies, federal vaccine committee reports, systematic reviews, meta-analyses and risk-of-bias analyses. The authors also reviewed studies from national safety monitoring programs which verify safety signals for hepatitis B vaccines licensed for the U.S. The report concludes there is no benefit related to vaccine safety or protection in a delayed first dose compared with getting it at birth. On the contrary, delaying the first dose increases the risk of getting hepatitis B in newborns.

Ameratunga R, et al. J Allergy Clin Immunol Pract. 2017(5): 1551-1555

Authors reviewed the diagnostic criteria for ASIA and looked into data that explains the cause of that syndrome. They found that patients with ASIA receiving a form of treatment called allergen-specific immunotherapy (IT) get 100 to 500 times more injected aluminum over 3 to 5 years, than people getting hepatitis B and human papillomavirus vaccines. The studies reviewed show that ASIA patients receiving IT had a lower incidence of autoimmune disease, which strongly indicates aluminum adjuvants do not cause or increase autoimmune disease in them. Further review of other study of patients with a different autoimmune condition (lupus) who had received the hepatitis B and HPV vaccines did not see exacerbation of their condition.

Schmuhl NB et al. Vaccine. 2020. 19; 38: 4038–4043

Authors found there is no link between getting the human papillomavirus (HPV) vaccine and infertility in women from the age group studied.

Glanz JM, et al. Pediatrics. 2021; 148:e2021051910

Researchers studied medical records from 584,171 children to learn if there was a link between receiving on-time vaccination (following the recommended immunization schedule) and children developing type 1 diabetes mellitus. They found vaccination did not increase the risk of children developing type 1 diabetes.

Wesselink AK, et al. Am J Epidemiol. 2022; 191(8): 1383-1395

Study authors found COVID-19 vaccination did not affect odds of achieving pregnancy in females. They also found that being infected with the virus that causes COVID-19 may lead to a brief decline in fertility for males. This means the vaccine is safe for females who want to get pregnant. It also means not getting the vaccine can affect the possibility of conceiving for males.

Taylor B, et al. The Lancet. 1999; 353: 2026-2029

Authors looked for any change in number or age of children diagnosed with autism associated with the MMR vaccine introduced in the United Kingdom in 1988. The study identified 498 cases of autism (261 "core" autism; 166 "atypical" autism; 71 "Asperger syndrome") in children born in the UK since 1979. There was a steady increase in autism cases by year of birth with no sudden change after the MMR vaccine was introduced. There was no difference in age at diagnosis between the cases vaccinated before or after 18 months of age and those never vaccinated. There was no causal relationship found between onset of autism within 1 or 2 years after vaccination with MMR. Developmental regression was not clustered in the months after vaccination.

Kaye JA, et al. BMJ. 2001; 322: 460-463

A United Kingdom study looked at links between MMR vaccination of children and rising prevalence of autism diagnoses in children. The study included 96 children with a pervasive developmental disorder born between 1992 and 1995 who received the MMR vaccine. They were compared with children who did not receive the vaccine. The study concluded the likelihood of autism was the same between children who received the MMR vaccine and those who didn't.

Mäkelä A, et al. Pediatrics. 2002; 110: 957–963

This study looked at 535,544 children aged 1-7 years old who were vaccinated between November 1982 and June 1986 in Finland. Researchers found there is no connection between MMR vaccination and encephalitis, aseptic meningitis or autism.

Madsen KM, et al. NEJM. 2002; 347: 1477-1482

In a population-based study in Denmark that included 537,303 children born between 1991 and 1998, Researchers found no link between autism and age at receipt of MMR vaccination, time since MMR vaccination, or date of MMR vaccination.

Institute of Medicine, The National Academies Press: 2004

An independent review committee found there is no causal relationship between the MMR vaccine and autism. The Institute of Medicine Immunization Safety Review on Vaccines and Autism involved input from 15 committee members with expertise in pediatrics, internal medicine, immunology, neurology, infectious diseases, epidemiology, biostatistics, public health, risk perception, decision analysis, nursing, genetics, ethics and health communications. The committee analyzed more than 200 relevant studies. The group also rejected a causal relationship between thimerosal-containing vaccines and autism.

DeStefano F, et al. Pediatrics. 2004; 113: 259-266

In this large case-control study, researchers compared MMR vaccination timing in a group of children with autism and a school-matched control group of children who did not have autism. They found no links between getting the MMR vaccine at the recommended age and an increased risk of conditions like plateau, regression or MR in the group of children with autism.

Klein KC, Diehl EB. Ann Pharmacother. 2004; 38: 1297-1300

Researchers identified and evaluated 10 articles on autism and the MMR vaccine. They didn't find any causal relationship between the vaccine and autism.

Honda H, et al. J Child Psychol Psychiatry. 2005; 46: 572-579

In a study of all children born between 1988 and 1996 in Yokohama, Japan, the number of new cases of autism spectrum disorder (ASD) increased significantly even though MMR vaccination decreased over the period. In addition, there was a steep increase in ASD that started with the 1993 birth cohort, the year after routine administration of MMR to Japanese children was discontinued. Authors concluded that the withdrawal of MMR vaccine did not lead to a reduction in the incidence of ASD and the vaccine can't explain the rise over time in the incidence of ASD.

Doja A, Roberts W. Can J Neurol Sci. 2006; 33: 341-346

In a review of literature on immunizations and autism, an overwhelming majority of studies concluded the MMR vaccine does not cause autism. Also, no convincing evidence was found to support a link between the vaccine preservative thimerosal and autism. In addition, no evidence was found to support chelation therapy for the treatment of autism.

Richler J, et al. J Autism Dev Disord. 2006; 36: 299-316

Authors found no evidence of a link between observable loss of skills (regressive phenotype) in autism spectrum disorder (ASD) and the MMR vaccine. This multi-site study used caregiver interviews to describe the loss of social-communication milestones. In addition, caregivers reported that the children with ASD had atypical development before the observable loss of skills.

Uchiyama T, et al. J Autism Dev Disord. 2007; 37:210-217

MMR vaccine and regression in autism spectrum disorders (ASDs) were not linked in a study of 904 patients with ASD in Japan. No significant difference was found in the incidence of regression between MMR-vaccinated children and non-vaccinated children.

Baird G, et al. Arch Dis Child. 2008; 93: 832-837

Researchers studied the cases of 98 vaccinated children aged 10-12 years in the UK with ASD and two control groups of similar age: 52 children with special educational needs but no ASD and 90 children in the "typically developing" group. There was no evidence of a different response to the measles virus or the measles component of the MMR vaccine in children with ASD, with or without regression, and children in the control groups who had either one or two doses of MMR. There was also no connection between autism symptoms and the concentration of antibodies against the measles virus.

Hornig M, et al. PLoS One. 2008; 3:e3140

Autism was not associated with traces of measles virus in the gastrointestinal tract after recovery from infection or MMR vaccination. In this study, researchers looked for measles virus in the guts of 25 children with both autism and gastrointestinal disorders, and another 13 children with the same gastrointestinal disorders but no autism. The virus was detected in one child from each group. No evidence of a connection between the presence of the measles virus in the gastrointestinal tract and autism was found.

Smith M and Woods C. Pediatrics. 2010; 125: 1134-1141

Researchers looked for any links between vaccines in the first year of a child's life and neuropsychological outcomes 7-10 years later. The study involved more than 1,000 children born between 1993-1997. On-time vaccination in the first year was compared with delayed or incomplete vaccination in the first year. The researchers found no negative effect on long-term neuropsychological outcomes in 42 different tests. The tests were related to speech and language, verbal memory, achievement, fine motor coordination, visuospatial ability, attention and executive-functioning tasks, behavior regulation, tics and general intellectual functioning. In fact, timely vaccination was associated with better performance on many outcomes.

DeStefano F, et al. J Peds. 2013; 163: 561-567

Researchers studied 321 children with diagnosis of autism spectrum disorder (ASD), autistic disorder (AD) or ASD with regression and 752 children not diagnosed with these conditions. They compared the number of components used in vaccines that each group of children had received through vaccines. Researchers wanted to find out if children with a diagnosis of ASD, AD or ASD with regression had received more vaccine components. Having a diagnosis of ASD, AD or ASD with regression was not associated with exposure to vaccine components at any of the studied time periods (birth to 3 months, birth to 7 months, birth to 2 years), or when comparing a how many vaccine components a child received in one day.

Taylor L, et al. Vaccine. 2014; 32: 3623-3629

Authors of a meta-analysis review of 10 studies (5 cohort and 5 case-control) involving over 1.25 million children looked at autism spectrum disorders (ASD), vaccines, the ingredient thimerosal (mercury) and the measles-mumps-rubella (MMR) vaccine. No causal association was found between vaccinations and ASD or between ASD and the MMR vaccine. In addition, no causal association was found between ASD and thimerosal (mercury).

Jain A, et al. JAMA. 2015; 313: 1534-1540

The study looked at MMR vaccine status in children with and without autism spectrum disorder (ASD) with older siblings with and without ASD. Relative risk was calculated for a child receiving an ASD diagnosis at ages 2 years, 3 years or 4 years based on 0 doses or 1 dose of MMR vaccine and whether the child had a sibling with ASD or a sibling without ASD. Relative risk also was calculated any child who got an ASD diagnosis at age 5 years based on 1) whether they had received 0 doses, 1 dose or 2 doses of MMR vaccine, and 2) whether the child had a sibling with ASD or a sibling without ASD. No harmful association was found between MMR vaccination and ASD risk. In addition, no causal association was found between receipt of 1 or 2 doses of MMR vaccine and having a higher risk of ASD for children with an older sibling with ASD.

Jaswa Eleni G, et al. JAMA Pediatrics. 2024; 178(3): 258-265

This cohort study included 2,261 and 1,940 infants aged 12 and 18 months, respectively, who were exposed to the COVID-19 vaccine in utero. Vaccination was not associated with abnormal neurodevelopmental scores on the Ages and Stages Questionnaire, third edition.

Hardie I, et al. The Lancet. 2025; 9(3): 162-171

Researchers looked for connections between SARS-CoV-2 infections during pregnancy, COVID-19 vaccination during pregnancy and early child developmental concerns in kids aged 13–15 months in Scotland. Concerns included communication, problem solving and development of social, emotional, behavioral and gross motor skills. Researchers analyzed data from 24,919 child-mother pairs. They did not find any connection between SARS-CoV-2 infection during pregnancy and developmental concerns in children. Instead, they found that getting the COVID-19 vaccine during pregnancy might reduce chances of developmental concerns about problem solving and emotional or behavioral development in children.

Hviid A, et al. JAMA. 2003; 290: 1763-1766

A study of 467,000 children born in Denmark between 1990 and 1996 compared children who were vaccinated with a thimerosal-containing vaccine with children who received a thimerosal-free formulation of the same vaccine. The risk of autism spectrum disorders was the same for children vaccinated with thimerosal-containing vaccine and for children vaccinated with thimerosal-free vaccine. The results do not support a causal relationship between childhood vaccination with thimerosal-containing vaccines and development of autism spectrum disorders.

Stehr-Green P, et al. Am J Prevent Med. 2003; 25: 101-106

A study compared the prevalence and incidence of autism in California, Sweden and Denmark from the mid-1980s to the late 1990s to the average exposures to thimerosal-containing vaccines. In California, the average thimerosal dose from vaccines increased throughout the 1990s. However, in Sweden and Denmark, exposure to thimerosal from vaccines was low during the 1970s and 1980s, decreased in the late 1980s and was eliminated in the early 1990s. In all three locations, the incidence and prevalence of autism spectrum disorders began to rise in the 1985-1989 period, and the rate of increase accelerated in the early 1990s. Findings do not support the theory that increased exposure to thimerosal-containing vaccines is responsible for the apparent increase in the rates of autism in young children observed worldwide.

Madsen KM, et al. Pediatrics. 2003; 112: 604-606

Researchers analyzed data from the Danish Psychiatric Central Research Register. They looked at all psychiatric admissions since 1971 and all outpatient contacts in psychiatric departments in Denmark since 1995. There was no trend toward an increase in the incidence of autism during the period when thimerosal was used in Denmark. From 1991 to 2000, after thimerosal was removed from vaccine in Denmark, the incidence of autism increased and continued to rise over the decade. There were also increases among children born after thimerosal was no longer used. Data do not support a correlation between thimerosal-containing vaccines and the incidence of autism.

Heron J, et al. Pediatrics. 2004; 114: 577-583

Researchers monitored the thimerosal exposure of more than 14,000 children born in the United Kingdom between 1991 and 1992. The age at which doses of thimerosal-containing vaccines were administered was recorded. Measures of ethylmercury from thimerosal by 3, 4 and 6 months of age were calculated and compared with numerous measures of childhood cognitive and behavioral development between 6 and 91 months of age. No evidence was found that early exposure to thimerosal had a negative effect on neurologic or psychological outcomes.

Fombonne E, et al. Pediatrics. 2006; 118: 139-150

This study looked at 28,000 children in Montreal, Quebec, Canada, born between 1987-1998, including 180 identified with pervasive developmental disorder (PDD), an older term for a group of conditions now diagnosed as Autism Spectrum Disorder. The study found that thimerosal and the MMR vaccine were not linked to the prevalence of PDD. Data ruled out an association between PDD and either high levels of ethyl mercury exposure or 1 or 2 dose MMR vaccinations.

Thompson WW, et al. NEJM. 2007; 357: 1281-1292

Researchers compared the frequency of 42 neuropsychological outcomes in 1,047 children ranging in age from 7 to 10 years who had early exposure to mercury from thimerosal-containing vaccines and/or thimerosal-containing immune globulin. The study did not support a causal association between early exposure to thimerosal used in vaccines or immune globulin and deficits in neuropsychological functioning at the age of 7 to 10 years old.

Schechter R, et al. Arch Gen Psychiatry. 2008; 65: 19-24

Autism data from the California Department of Developmental Services were analyzed between 1995-2007. Thimerosal was removed from recommended childhood vaccines after 2002. However, autism cases continued to increase each quarter after the removal of thimerosal. Data did not support the hypothesis that exposure to thimerosal during childhood is a primary cause of autism.

Price C, et al. Pediatrics. 2010; 126: 656-664

Researchers reviewed managed care organization records and conducted interviews with the parents of 256 children with autism spectrum disorder (ASD). They also studied another 752 children without autism, matched to the ASD children by birth year, gender and managed care organization. Prenatal and early-life exposure to mercury from thimerosal-containing vaccines and immune globulin was not related to increased risk of ASDs.

Budzyn D, et al. Pediatr Infect Dis J. 2010; 29: 397-400

Researchers in Poland compared the vaccination history of 96 children with autism, age 2 to 15 years, and 192 children without the disorder. No causal relationship was found between receiving the measles-mumps-rubella (MMR) vaccine and the development of autism. In fact, children later diagnosed with autism who were vaccinated before the diagnosis was made had a lower autism risk than those who were not vaccinated. The result was similar for children who received a single-antigen measles vaccine.

Mitkus RJ, et al. Vaccine. 2011; 29(51): 9538–9543

This study compares the amount of aluminum from vaccines and diet during an infant's first year of life with the safe amount of aluminum indicated by the Minimal Risk Level (MRL) model. Researchers concluded that exposures to vaccines with aluminum adjuvants are extremely low risk for infants. They also concluded that the benefits of getting those vaccines outweigh any potential concerns.

Karwowski MP, et al. Acad Pediatr. 2018; 18: 161-165

Researchers studied the potential connection between the amount of aluminum found in the body and infant development in a group of children 9 to 13-month-old form an urban primary care center. They used the Bayley Scales of Infant and Toddler Development to measure development, and linear regression models to measure aluminum load. Researchers found there was no connection between the amount of aluminum in children's bodies and their immunization history or their language and cognitive development.

Andersson NW, et al. Annals of Internal Medicine. 2025; 178(10): 1369-1377

Researchers analyzed information from over 1.2 million two-year-old children born in Denmark between 1997 and 2018. They compared national data on childhood vaccinations, outcome diagnoses and potential confounding variables for those children. The amount of aluminum in childhood vaccines varied over time. They did not find evidence supporting an increased risk for autoimmune, atopic or allergic or neurodevelopmental disorders associated with early childhood exposure to aluminum-containing vaccines.

Nirenberg E, et al. Pediatrics. 2025; doi:10.1542/peds. 2025-074874

Researchers break down how decades of research show that aluminum adjuvants are safe and are not linked to autism, asthma or autoimmune disorders in children. The report compares aluminum exposure from vaccines with everyday sources of aluminum. Authors note that the entire AAP recommended immunization schedule has significantly less aluminum than a single dose of antacid medication, for example. The report also answers safety concerns that parents have about vaccines. Evidence from the strongest studies with more than a million children involved have consistently found there is no link between aluminum toxicity and vaccines.