A large Danish study confirms aluminium in childhood vaccines does not pose health risks
Analyses of data of over 1.2 million children born in Denmark between 1997 and 2018 did not find evidence supporting an increased risk for autoimmune, atopic or allergic, or neurodevelopmental disorders associated with early childhood exposure to aluminium in vaccines
A landmark study analysing the data of 24 years (1997-2020) of over 1.2 million children born in Denmark between 1997 and 2018 did not find evidence supporting an increased risk for autoimmune, atopic or allergic, or neurodevelopmental disorders associated with early childhood exposure to aluminium-adsorbed vaccines. As of 2023, vaccination coverage in Denmark during the first two years of life is as high as 94-97%.
Aluminium has been used as an adjuvant to enhance the immune system response for about 70 years. Despite its long use, the safety of aluminium has been questioned by anti-vaccination campaigners, leading to doubts about vaccine safety. Concerns about vaccine safety arising from the use of aluminium has not been fully addressed as large-scale safety data had remained limited. The large-scale study carried out by researchers from Statens Serum Institut, Copenhagen, and University of Copenhagen, Copenhagen, Denmark has finally addressed the safety of aluminium-containing vaccines. Results of the study have been published in the Annals of Internal Medicine.
In response to readers comments, Christine Laine, who is Editor of Annals of Internal Medicine writes on the journal website: “Annals found Andersson and colleagues’ study to be among the strongest research currently available to address the important question of whether there is an association of the dose of vaccine-associated aluminium exposure and chronic conditions in early childhood. Clinicians and the public need information from large, carefully done studies for thoughtful decision-making about vaccines.”
50 chronic disorders studied
The researchers used the data on childhood vaccinations available with Denmark’s nationwide registry data and linked the health outcomes from each vaccination over the years. They looked at the incidence of 50 chronic disorders, including autoimmune (dermatologic, endocrinologic, hematologic, gastrointestinal, and rheumatic), atopic or allergic (asthma, atopic dermatitis, rhinoconjunctivitis, and allergy), and neurodevelopmental (autism spectrum disorder and attention deficit–hyperactivity disorder). As per the paper, children born between January 1, 1997 and December 31, 2018 were included, and the authors followed children from two years of age until December 31, 2020, or until they reached age five years, died, or were lost to follow-up, whichever came first.
They found that “cumulative aluminium exposure from different vaccinations during the first two years of life was not associated with increased rates of any of the 50 disorders assessed”. “The nationwide cohort study did not find evidence supporting an increased risk for autoimmune, atopic or allergic, or neurodevelopmental disorders associated with early childhood exposure to aluminium-adsorbed vaccines. For most outcomes, the findings were inconsistent with moderate to large relative increases in risk, although small relative effects, particularly for some rarer disorders, could not be statistically excluded,” the authors write.
The registry contains comprehensive information of all infants and parents, which helps identify potential confounders at both the child and maternal level (for example, preterm birth, household income, and maternal medical history). Children diagnosed with certain congenital or preexisting conditions (including congenital rubella syndrome, respiratory conditions, primary immune deficiency, and heart or liver failure) were excluded before undertaking data analysis.
Quasi-experimental framework
As per the authors, in the last 25 years, new vaccines have been added, periodic substitutions of certain vaccines due to supply shortages have occurred and older vaccines have been replaced with newer formulations. As a result, the cumulative aluminium exposure through vaccination at age two years varied by birth year — the total exposure ranged from 0 to 4.5 mg, and the median was 3 mg. The authors utilised the “systematic variations in aluminium exposure” through early childhood vaccination to provide a natural “quasi-experimental framework” for estimating the effect of aluminium exposure from vaccination on health outcomes.
The study did not include a control group of children who did not receive vaccinations as only 2% (15,237) of children are unvaccinated, which is “too small for meaningful comparison”, Anders Peter Hviid, head of the epidemiology research department at the Statens Serum Institut in Denmark and the first author of the study told Reuters. The study instead used the random variation in aluminium exposure through vaccination to understand the safety concerns of aluminium in vaccines.
The Annals of Internal Medicine Editor-in-Chief Christine Laine says in the Comments section: “Like all observational research, this study has limitations. Researchers can mitigate (though rarely eliminate) such limitations through different methodological approaches, all of which have different tradeoffs. Scientists may disagree on the best approach to address a given research question. Often no approach is unequivocally best; they either have different trade-offs or address different questions.”
Responses to comments
In response to comments to the paper, the authors respond to the question of not including children who did not receive any vaccine as a control group. The authors say: “The small size of this group would also increase the statistical uncertainty in any categorical comparisons with them. For these reasons, unvaccinated children do not serve as a suitable reference group when studying these particular outcomes. Instead, our main analysis evaluates the dose-response relationship within the range of aluminium exposure from early childhood vaccination observed in Denmark during the study period.”
In response to another comment on not including unvaccinated children in the analyses, the authors note: “Our main analyses did not exclude unvaccinated children. However, excluding unvaccinated children in subsequent sensitivity analyses yielded results consistent with our main findings.”
In response to another criticism that follow-up started only after children became two years of age, the authors write: “Since we examine incident events during follow-up, children with records of the outcome of interest before age two must be excluded.” They then add: “We do provide a supplementary analysis with follow-up starting at age 14 months, which showed results similar to those of the main analysis… Many of these outcomes cannot be reliably diagnosed in infancy. This includes key outcomes such as autism and asthma. Starting follow-up at age two helps ensure that exposure levels have been set and allows for the expected lag between symptom onset and diagnosis for most outcomes.”
In response to another question that autism is far more likely to be diagnosed in the outpatient setting and so restricting the study outcome measures that are captured by hospital diagnoses may miss out autism cases, the authors note: “In Denmark, general practitioners act as gatekeepers to specialist diagnoses and care, which is often provided within the hospital system. Autism diagnoses are predominantly made by specialists in the hospital system, which in Denmark also includes outpatient services.”
The Annals of Internal Medicine Editor-in-Chief Christine Laine acknowledges the comments by readers who have pointed out “marginally significant associations with some neurodevelopmental conditions” observed in secondary analyses. Christine Laine says: “Secondary analyses explored over 540 comparisons, so it is expected that some are likely to be statistically significant by chance alone. The editors agree with the authors’ approach of basing conclusions on the primary adjusted analyses that are the most rigorous and valid.”
Robert Kennedy decries study
Describing the study “deeply flawed” that it “functions not as science but as a deceitful propaganda stunt by the pharmaceutical industry,” Robert F. Kennedy Jr., Secretary of the U.S. Department of Health and Human Services (HHS) said in an Opinion article published on Trial Site that the “architects of this study meticulously designed it not to find harm”. Many of his concerns are similar to the ones raised by scientists in the journal such as no including unvaccinated children, relying only on hospital diagnoses thereby missing autism cases etc.
Saying that the “does not just suffer from mere methodological limitations. Its design flaws are defining. The only thing this study proves is the thorough corruption of the scientific journals that publish such garbage-in, garbage-out exercises in statistical manipulation,” Kennedy wanted the journal to “immediately retract” the “badly flawed study”.
Author’s rebuttal
Responding to the criticism by Kennedy, Anders Hviid from the Department of Epidemiology Research, Statens Serum Institut and a coauthor of the paper writes in rebuttal on Trial Site that HHS Secretary “raises a number of methodological concerns, couched in needlessly vitriolic rhetoric”, and that many of 11-odd methodological concerns raised by him have already been posted on the journal website and have been “responded to already”. “The claim that we have designed this study to find no association can be easily refuted,” writes Anders Hviid. Explaining the reason, he writes that unlike the U.S. study that observed a “dose-response association between aluminium exposure from vaccines and asthma by five years of age”, the current study “could not replicate” the U.S. finding and that the current study is a “further evolution of this design with more study outcomes than just asthma”.
Anders Hviid concludes saying: “Our study does not provide support for the hypothesis that aluminium used as adjuvants in vaccines are associated with increased risks of early childhood health conditions. None of the critiques put forward by the Secretary is substantive.”
No retraction
Rejecting Kennedy’s call for retracting the study, Christine Laine, Editor-in-chief of the journal told Reuters: “I see no reason for retraction.” Acknowledging that some of the issues raised by Robert Kennedy underscore the “acceptable limitations” of the study, “they do not invalidate what they found, and there’s no evidence of scientific misconduct”, Christine says. According to Reuters, the journal “does not intend to respond directly to Kennedy’s piece, which was not submitted to the Annals,” while it plans to “respond to criticism the article has received on its website”.
