Thursday, 18 May 2017

On vaccinated and un-vaccinated homeschooled children: the disappearing-reappearing-disappearing-reappearing studies


I originally began writing this post in the last week of November 2016 following first sight of the study abstract by Anthony Mawson and colleagues [1] and their journey into a topic that has had its fair share of discussion/argument* (*delete as appropriate) with autism in mind down the years: are vaccines or immunisation patterns potentially linked to [some] autism?

As it happened, this post was shelved for some time because (a) only an abstract appeared despite a publication date accompanying the initial open-access submission in a Frontiers journal and (b) the subsequent sudden disappearance of the abstract from the publishers website following some discussions on social media about the paper and the review process (see here and see here for more information).

The study then appeared in a different journal (April 2017) before once again disappearing.

Now it's back - for now - in the same journal, so once again it's fodder for this blog...

As I always do when it comes to any chatter specifically on this topic, I should reiterate a few things: (a) the prime directive of this blog - no clinical or medical advice is given or intended - and (b) that vaccines save lives. I know some people attribute other factors to that 'life-saving' angle when it comes to vaccines over the longer term (better health, better environment, etc), but one really only needs to look at the protective effect of the various meningitis vaccines for example, to see their results in something like real-time. I repeat again: vaccines save lives.

What however does seem to be missing from at least some of the general discussion about vaccines as a whole and their very positive health effects is the fact that they are medicines. As such they are not somehow impervious to potentially producing side-effects for some people, albeit a small proportion of people who use them. The problem at the moment is, that we don't really know everything there is to know about which people might be at greater risk of side-effects than others (although some clues are emerging) and importantly, how all those side-effects may manifest. Science - metabolomic science - is however starting to tackle some aspects of these issues [2] minus too much hype at the present time.

As per the title of this post, Mawson et al set about examining whether there were differences between those children who were vaccinated and those un-vaccinated across "a broad range of health outcomes." In line with the previous history hypothesising about autism and specific vaccination, the authors focused on any 'association' between vaccination status and neurodevelopmental disorders (NDD) taking into account other potentially confounding variables.

The source data for those vaccinated / un-vaccinated children participants (N=666) was an anonymous online questionnaire completed by mothers of children who were members of various homeschooling organisations in four regions of the United States. Homeschooling refers to a situation where a child is educated at home outside of the mainstream education system choices. Homeschoolers were selected for study because, according to the authors, a "higher proportion are unvaccinated compared to public school children."

Results: around 40% of the participants were indeed described as un-vaccinated in the Mawson cohort. This is quite a bit higher than other estimates [3] specifically looking at homeschooled children. Then to some of the details: "Vaccinated children were significantly less likely than the unvaccinated to have been diagnosed with chickenpox and pertussis." If you needed more evidence that vaccines work, that last sentence kinda provides you with it, particularly in light of what diseases like pertussis can potentially do to the most vulnerable.

And then some potential controversies: vaccinated children were significantly more likely to have been diagnosed with pneumonia, otitis media, allergies and NDDs (defined as autism spectrum disorder, attention deficit hyperactivity disorder, and/or a learning disability). After some statistical adjustment for potentially confounding variables, authors reported that "vaccination, nonwhite race, and male gender were significantly associated with NDD after controlling for other factors." I might also draw your attention to the reported finding that: "preterm birth and vaccination combined was strongly associated with NDD in the final adjusted model with interaction, more than doubling the odds of NDD compared to vaccination alone." This might suggest that there are synergistic variables at work influencing any identified risk continuing a research theme [4]. Indeed, the same authors have devoted a whole other article to this finding [5] (this paper also went through the same disappearing-reappearing act too).

Wearing the objective blinkers of science, this is by no means perfect research. Not only are there potential issues related to the use of an on-line questionnaire (and anonymous at that), the focus on subjective reports over inspection of more objective medical records (even though parents were asked to obtain and use their child's vaccination record(s) when completing the questionnaire), and problems associated with recall (including possible telescoping effects), there are a whole host of other issues that one could cite in relation to such research and potential biases that could/might have influenced the results (including factors such as this one). I might also add that the Mawson study did not appear to 'name names' when it came to which individual vaccines may or may not have been involved in their findings despite asking questions about if and when specific immunisations were administered to participants. Indeed authors noted: "We did not set out to test a specific hypothesis about the association between vaccination and health." Then there is also the 'reaction' angle to papers such as this one to mention; bearing in mind that science these days does not exist in some sort of social/cultural vacuum as per other very recent and very relevant examples. Cumulatively, you can see that there are issues and factors to consider, as there are in relation to other investigations in this still contentious area (see here).

Does then the Mawson paper therefore provide definitive proof of any link between vaccination status and NDDs including autism? No it doesn't, bearing in mind that science generally deals in probabilities over and above 'proof'.

Does the Mawson paper provide any relevant information on vaccination status and the variety of health outcomes included for questioning? Well, on this point I'm gonna cautiously say maybe; at least with the requirement for further scientific investigation. Bearing in mind the caveats discussed previously, it is interesting that the authors' analysis of those fully vaccinated, partially vaccinated and not-vaccinated for example, suggested something when it comes to risk of things like allergic rhinitis, ADHD, eczema, a learning disability, and NDD in a sort of dose-related pattern. This of course, could be due to chance, but without further study we don't or won't know. Yes, I know that the 'too many, too soon' question has already been discussed in the peer-reviewed domain and hasn't stood up well to scrutiny (see here) but perhaps further studies are indicated to confirm/refute such dose-related findings and if necessary, identify any potentially relevant mechanism that might be at work? I say all that with the realisation that something like allergy and atopic disease already has a potentially interesting relationship to the presentation of ADHD (see here) and/or [some] autism (see here).

Within the context of quite a lot of research indicating that, at a population level, vaccinations are pretty safe medicines and probably not linked to autism (possibly even protective when delivered under certain circumstances [6]) one has to be careful not to inflate the Mawson findings above what they currently represent on the hierarchy of scientific evidence. This was, by no means, perfect research. The fact however that this topic continues to be discussed in various parts of society (including the peer-reviewed domain) suggests that science might still have an important role to play in this area particularly in the context of the pluralised autisms (and other labels) and taking into account some chatter a while back about various 'kingdoms of autism'. But such investigations need to be done with care and without grand, sweeping statements being made that could undermine the vital service that immunisation provides to the population as a whole. The associated use of seemingly under-vaccinated populations such as homeschoolers for example, might also represent something of an 'under-used' natural research cohort to further enable more rigorous science to be conducted into such 'hot potato' research areas...

To close, and without too much chatter, Roald Dahl and his experience of measles. Not to scare, not to name-call, not to stigmatise, just to remember a time when measles was rife and for some, measles was deadly.

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[1] Mawson AR. et al. Pilot comparative study on the health of vaccinated and unvaccinated 6- to 12-year-old U.S. children. J Transl Sci 2017. 3.

[2] McClenathan BM. et al. Metabolites as biomarkers of adverse reactions following vaccination: A pilot study using nuclear magnetic resonance metabolomics. Vaccine. 2017; 35: 1238–1245.

[3] Thorpe EL. et al. Homeschooling parents’ practices and beliefs about childhood immunizations. Vaccine. 2012; 30:  1149–1153.

[4] Wang C. et al. Prenatal, perinatal, and postnatal factors associated with autism: A meta-analysis. Medicine (Baltimore). 2017 May;96(18):e6696.

[5] Mawson AR. et al. Preterm birth, vaccination and neurodevelopmental disorders: a cross-sectional study of 6- to 12-year-old vaccinated and unvaccinated children. J Transl Sci. 2017; 3.

[6] Berger BE. et al. Congenital rubella syndrome and autism spectrum disorder prevented by rubella vaccination - United States, 2001-2010. BMC Public Health. 2011; 11: 340.

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ResearchBlogging.org Anthony R Mawson, Brian D Ray, Azad R Bhuiyan, & Binu Jacob (2017). Pilot comparative study on the health of vaccinated and unvaccinated 6- to 12-year-old U.S. children Journal of Translational Science : 10.15761/JTS.1000186