Yet more evidence that the antivaccine trope of “too many too soon” is nonsense

One of the more persuasive talking points repeated ad nauseam by the antivaccine movement is the “too many too soon” trope. The idea behind this bit of propaganda is that, thanks to the expansion of the childhood vaccine schedule over the last 30 years, today’s children are getting too many vaccines too soon, and these vaccines “overwhelm” the infant’s immune system, leading to all the dire conditions and diseases for which antivaxers blame vaccines: autism (even in dogs!), asthma and autoimmune diseases, premature ovarian failure, diabetes, sudden infant death syndrome (SIDS), the deaths of young people, and even abusive head trauma (previously known as shaken baby syndrome). Part and parcel of this idea is that unvaccinated children are healthier than vaccinated children, no matter how low into the muck of pseudoscience antivaxers have to go to dredge up “evidence” to support this idea.

The idea of “too many too soon” makes “intuitive” sense in that to the layperson it would seem that throwing too many challenges to the immune system in too short a time in a developing baby might be harmful, but we have copious evidence that this is not so. For one thing, even though there are more vaccines, the design and manufacture of vaccines are much more precise, such that the number of antigens children receive today by age 4 is at least 25-fold fewer than it was 30-40 years ago even as children receive vaccines against many more diseases. When you compare the number of antigens in the vaccine schedule (a few hundred at most) to the many thousands of antigens they encounter just by living, the ridiculousness of the “too many too soon” talking point becomes obvious. It’s not just that, though. Scientists have actually done studies. For instance, in 2013 a study was published showing no association between total antigen exposure and the risk of autism or maximum antigen exposure at one visit (number of shots given in a single visit) and autism risk. It was about as resoundingly negative a study as I’ve ever seen. Basically, the current vaccine schedule is safe and effective and evidence-based.

So is the one that I’m going to talk about here, one that I discovered from Twitter and news reports:

Vaccines don't overload babies' immune systems, study finds – https://t.co/ROt2oihdBf

— Maggie Fox (@maggiemfox) March 6, 2018

The aerial view of the study shows the following:

Some parents may be afraid that babies and toddlers get too many vaccines all at once, but a new study can help put such worries to rest.

It found that kids who got more vaccines were not any more likely to get unrelated infections than kids who got fewer vaccines, or who had them spaced out more than recommended.

There was not much reason to think that vaccinating children might make them somehow more susceptible to diseases in general, but the researchers said it is important to keep testing, to reassure parents.

OK, before I start discussing the study itself, let me just express my irritation at this framing of the reason to keep testing, to reassure parents. While this might be somewhat true for fence sitters, those who’ve heard the lies of antivaxers and become concerned because they don’t know whether the fear mongering has any basis in science and evidence, but even to reach them probably doesn’t make continuing to do these studies over and over again justifiable, either scientifically or ethically, once the evidence has become overwhelming that vaccines to not “overwhelm” babies’ immune systems. The reason is simple. The parents responsible for the myth of “too many too soon” will not be reassured by a study. They will not be reassured by five negative studies. They will not be reassured by 50 negative studies. They will not be reassured by 5,000 negative studies. Hell, they probably won’t be reassured by 5 million negative studies. Worse, they’ll continue to spread antivaccine misinformation that will continue to influence a subset of parents to start to doubt vaccines.

End of mini-rant. On to the study, which was published in JAMA yesterday by Glanz et al and entitled Association Between Estimated Cumulative Vaccine Antigen Exposure Through the First 23 Months of Life and Non–Vaccine-Targeted Infections From 24 Through 47 Months of Age. Basically, it’s a nested case-control study that looks at whether there is a difference in antigen exposure between children with non-vaccine-targeted infections compared with children without the infections. Cumulative vaccine antigen exposure, estimated by summing the number of
antigens in each vaccine dose received from birth through age 23 months, was compared.

The children making up the cases and controls were taken from a cohort drawn from the Vaccine Safety Datalink (VSD). Antivaxers often claim that the Vaccine Adverse Event Reporting System (VAERS) is a passive system and, as such, can miss many adverse events and lament the absence of an active reporting system. By “passive” reporting system, I mean one that doesn’t actively look for cases and relies on parents and health care providers reporting adverse events. In contrast, “active” systems look for cases actively by looking for them, either through a database or other means. VSD is an active surveillance system. Yes, contrary to a frequent antivaxer claim that there are no active surveillance systems for vaccine safety looking for adverse events. There are, in fact, three: one run by the FDA called PRISM (Post-licensure Rapid Immunization Safety Monitoring System) and the VSD (Vaccine Safety Datalink), which is run by the CDC, and the Clinical Immunization Safety Assessment (CISA) Project, which studies of vaccines safety with an emphasis on those who might be at risk of adverse events—something antivaccine activists say isn’t done.

So here’s how cases were identified:

VSD data sets were first used to identify children born between January 1, 2003, and September 31, 2013. For inclusion, children had to be continuously enrolled in the health plan from age 6 weeks through 23 months. Children were excluded if they did not have at least 2 well-child visits before their first birthday, had a medical contraindication to vaccination, or if they had received vaccines not universally recommended by the Advisory Committee on Immunization Practices.10 Eligible children were followed up through age 47 months or until disenrollment from their health care organization; the final day of follow-up was December 31, 2015.

Then to identify cases of non-vaccine-preventable infections:

From ages 24 through 47 months, potential non–vaccine-targeted infections were identified in VSD data sets using International Classification of Diseases, Ninth and Tenth Revisions, Clinical Modification (ICD-9/10-CM) codes in the ED and inpatient settings (eTable 1 in the Supplement). The list of outcome ICD codes was based on a Danish cohort study by Sørup et al,¹¹ which tested a similar hypothesis. Non–vaccine-targeted infection outcomes included lower respiratory infections, upper respiratory infections, gastrointestinal infections, and other viral and bacterial infections. In the cohort, the first occurrence of an ICD code for a non–vaccine-targeted infection from ages 24 through 47 months was identified as a potential incident case.

You don’t have to go into all the epidemiology-speak, but you do have to know what a case control study is, because that’s what this is. In a case control study, cases (patients with a disease or condition under study) are matched as closely as possible in pertinent risk factors (e.g., age, sex, race, other risk fctors) to controls who do not have the disease or condition. Then, the two groups are compared for differences in a specific risk factor for which they were not matched. You don’t need to know the details, but you should know that each case was matched to up to four controls, and that ultimately there were 193 cases with non–vaccine-targeted infections and 751 controls without non–vaccine-targeted infections studied. Antigen exposure was measured as the number of immunogenic proteins and polysaccharides in each vaccine (eTable 3 in the Supplement).

So what did they find. Figure 2 shows the odds ratio for non-vaccine-targeted diseases

Notice the plot on the right. Notice how all the error bars cross 1.0. That means there was no statistically significant difference between cases and controls in the chance of getting a disease not targeted by vaccines. In other words, cumulative exposure to antigens did not correlate with these diseases. Neither did another factor commonly invoked by antivaxers:

That’s right. The estimated maximum single-day antigen exposure doesn’t correlate with the risk of disease not targeted by vaccines either. The authors did a number of secondary analyses and confirmatory analyses to make sure that they didn’t miss anything, and they didn’t.

Will this study reassure antivaxers? Of course not. It might reassure some fence sitters, but the hard core antivaxers will not be swayed. Even the publishers of JAMA seem to know this, as the editor published an accompanying editorial by Sean O’Leary, MD and Yvonne Maldonado it’s noted:

When the VSD system was created in 1990, its charge was 2-fold: to study vaccine safety and to strengthen the public’s confidence in vaccines. The study by Glanz et al9 is an example of fulfilling the first charge. However, the VSD has not been as successful at strengthening the public’s confidence in vaccines. The rates of vaccine refusal and delay have increased, and clinicians encounter vaccine-hesitant parents with increasing frequency.3,4

The present study provides further reassurance to parents that the US childhood vaccination schedule is safe in terms of not being associated with an increased risk of non–vaccine-targeted infections, yet the small but vocal minority of antivaccine groups may not be satisfied by the evidence provided through VSD and other vaccine safety surveillance. For example, insistence by such groups that vaccines cause autism persists, despite overwhelming science to the contrary. Although the VSD and other mechanisms, such as the Post-Licensure Immunization Safety Monitoring system, must continue to study the scientific questions, closer attention must also be paid to fulfilling the VSD’s second purpose of strengthening the public’s confidence in vaccines.

This passage bothers me. The purpose of the VSD is primarily scientific, to identify adverse reactions to vaccines through active surveillance. O’Leary and Maldonado are naive in the extreme if they think any number of scientific studies are going to reassure antivaxers. We already have more than enough studies to know that vaccines don’t cause autism or any of the other conditions antivaxers blame them for. We know that vaccines are safe and effective. That is not to say that we shouldn’t continue to study them through the VSD, looking for adverse reactions, but reinventing the wheel by doing in essence the same study over and over and over again and getting negative results over and over and over again are not the answer. Finding better ways to communicate those findings to the public is. In particular, we need to recognize that the hard core antivaxers will not be swayed by anything that comes out of the VSD or any other government-maintained database. That’s why it’s important to inoculate (if you’ll excuse the term) those who might be susceptible to the antivaccine message against the misinformation and pseudoscience that drive the antivaccine movement.