A new study suggests there may be a link between aluminum used in vaccines that are given to young children in the first two years of life and the risk of developing asthma before age 5. The findings are preliminary and both the authors and others who have studied the data urge caution in the interpretation of the results.
Based on the findings, the possible association needs to be further explored, said the authors, who nonetheless are worried that in an era of rampant vaccine misinformation and expanding hesitancy on the part of some parents, results that should be seen as the start of a scientific exploration may instead be viewed as the conclusion of it.
Matthew Daley, the first author of the study, published Tuesday in the journal Academic Pediatrics, said the results will not change how he practices medicine.
“I practice as a pediatrician and … I need to feel comfortable that I’m doing best by the kids that I’m vaccinating,” Daley, a senior investigator at the Institute for Health Research at Kaiser Permanente Colorado, told STAT in an interview. “And I’m still going to advocate for vaccines as strongly as I did before we had these findings.”
The Centers for Disease Control and Prevention, which funded the study, said it will not alter its recommendations on vaccines that should be given to children based on this one study, noting in a statement that previous studies have not found a link between childhood vaccines and asthma. The CDC, the Food and Drug Administration, and the National Institutes of Health are in discussions about what additional studies should be conducted to further investigate the issue.
In an emailed statement, the CDC said an increase in asthma among young children predated the addition of aluminum to vaccines, which occurred in 1991. The increase in asthma, based on data from the National Health Interview Survey, was first observed in 1980. The agency noted that many factors that couldn’t be measured in this study might increase a child’s risk of developing asthma.
“We hope that additional studies can quickly provide more clarity, but at least from the national trend data, it appears that addition of aluminum-adjuvanted vaccines do not account for the overall trends that we see,” the agency said.
Daley and colleagues undertook the work after a 2013 report on vaccine safety from the Institute of Medicine — since renamed the National Academy of Medicine — urged additional study of whether there might be a link between exposure to aluminum in vaccines and the development of asthma.
“There’s a theoretical possibility that aluminum could increase allergy risk. But I’d highlight that it’s theoretical and it’s based on fairly limited animal data,” Daley said.
Aluminum is used in a number of vaccines as an adjuvant — a way to boost the immune response the product triggers. The practice has been used for decades. Vaccines that young children receive that contain aluminum include: diphtheria, tetanus, and acellular pertussis; hepatitis B; some formulations of Haemophilus influenzae type B or Hib vaccine; and pneumococcal conjugate vaccines.
Covid-19 vaccines and flu shots do not contain aluminum, the CDC said in its statement.
All young children are also exposed to other sources of aluminum, which is found in breast milk, infant formula, and foods. That fact is one of a number that complicates investigating whether there is a link between aluminum in childhood vaccinations and asthma, the study said, though the authors noted that a 2019 report said it appears that little or no aluminum that is ingested from dietary sources is absorbed through the gastro-intestinal tract.
The new study is based on a large group of children — nearly 327,000 — which is a point in its favor. But this is not a clinical trial, where some children received an intervention and the others received a placebo. Here the researchers conducted what is called a retrospective observational study, scouring the medical records of the children involved.
Observational studies cannot prove that something caused something else. They can only detect if there appears to be an association — or an absence of one — between a health outcome and a drug or vaccine, a food or an activity, such as smoking or exercising.
As such, it’s impossible to quantify at this point how much, if at all, an individual child’s risk of developing asthma might increase due to receipt of these vaccines.
“The incidence of persistent asthma in children less than 5 years of age is about 3.8%, and there are different estimates from different data sources,” Daley said via email. “So if these study findings are replicated in other studies, the implication is that reducing aluminum could reduce asthma risk below 3.8%. By how much is difficult to say, because asthma has many environmental triggers.”
The children studied were born between the start of 2008 and the end of 2014 and received care at seven sites across the country that participate in the Vaccine Safety Datalink, a network of health institutions that collaborate with the Centers for Disease Control and Prevention to study vaccine safety.
The researchers divided the children into two groups — those who had eczema by 12 months of age and those who did not. Eczema is a form of allergic disease, as is asthma. So children with eczema might be predisposed to develop asthma at higher rates than children who don’t have eczema, regardless of how much exposure either group had to aluminum in vaccines.
“If there’s any relationship between aluminum and asthma, it could look different in kids with eczema than kids without eczema,” Daley explained.
The researchers amassed data on how many vaccinations each child in the cohort received before they turned 2, using those data to estimate each child’s exposure to aluminum. They then looked to see which children developed persistent asthma between the ages of 2 and 5. Their definition of persistent asthma — which can be hard to diagnose — was having had one inpatient or two outpatient health care encounters with a diagnosis code for asthma, and having used two or more long-term asthma control medications.
Six percent of the children who had eczema developed asthma compared to 2.1% of the kids who didn’t have eczema. The analysis suggested there was a positive association between the amount of aluminum exposure and the development of asthma for both groups of children.
The researchers ran a number of secondary analyses to try to determine if some factors they couldn’t control for could have been influencing the results in ways that would create the illusion of an association where one didn’t actually exist. None of those analyses discounted the findings, though the scientists noted there were some factors they had no information on, such as whether children who developed asthma came from families with a history of asthma, or from households in which they were exposed to secondhand smoke.
The researchers concluded the issue deserves more study — a position echoed by several experts who were not involved in the work but who reviewed it. Those outside experts also sounded cautionary notes.
“I think this is just another example where explaining science to the public is challenging,” said Ed Belongia, director of the Center for Clinical Epidemiology and Population Health at Wisconsin’s Marshfield Clinic Research Institute.
“This is a well-designed study. It needs to get out there, and other people need to be looking at this issue. But one study is almost never definitive.”
All researchers know that — especially with observations studies — there is a chance that findings will simply turn out to be faulty, even when the trials are well-designed. Belongia has first-hand experience with this reality.
After the 2009 H1N1 flu pandemic, the CDC wanted to ensure that flu shots targeting the new subtype of flu were safe to give to pregnant women. Belongia and colleagues conducted a study that found — to the dismay of everyone involved — that there appeared to be an increased risk of miscarriage among women who had been vaccinated with the newly formulated flu shots in both the 2010-2011 and 2011-2012 seasons. Women who had not received a flu shot in the year before their pregnancy didn’t appear to be at elevated risk of miscarrying.
The CDC ordered a larger follow-up study, which did not detect any association between flu shots during pregnancy and a risk of miscarriage.
“We need to follow the evidence wherever it leads. But there will be some blind alleys where we go down a path, and we don’t find anything there. In this case we don’t know yet,” said Belongia. “If multiple studies in different populations are all giving you the same answer, that’s a clue that you’ve got something real going on here.”
Michael Osterholm, director of the University of Minnesota’s Center for Infectious Disease Research and Policy, pointed to research he was involved in in the 1980s, where studies of vaccines to protect against haemophilus influenzae type B produced wildly discordant results in different parts of the country, with the findings in Minnesota showing no benefit.
“At one point, people were saying … ‘Don’t give these haemophilus vaccines. They provide no benefit and may actually be dangerous for the children,’” Osterholm noted. “Well today, because of that vaccine we virtually have reduced haemophilus influenzae type B meningitis to a very, very low level in this country.”
Andrew Racine, a professor of pediatrics at Albert Einstein College of Medicine and chief medical officer at Montefiore Medicine in New York City, wrote a commentary on the study that opened with a quote attributed to Ralph Waldo Emerson: “People only see what they are prepared to see.”
Racine suggested there are reasons to be cautious about the findings, but concluded that even if the study raises uncomfortable questions about the safety of some vaccines, more research into this issue must be pursued, saying that “as scientists, as stewards of public health, we must be ‘prepared to see’ possible complications from their use.”
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