Evaluation of Immunization Rates and Safety Among Children with Inborn Errors of Metabolism

2 Nov

Ever since the Hannah Poling case became public, and especially give the way in which David Kirby has presented the case, there has been a question of whether vaccines can cause regressions in children with inborn errors of metabolism (mitochondrial disorders are a subset of these).

I discussed one very recent paper Fever Plus Mitochondrial Disease Could Be Risk Factors for Autistic Regression. Commenter and LBRB blogger Joseph made the very correct observation then:

I’d say it’s potentially interesting, but limited. In order to tell that something is a risk factor, you need a case-control study.

More specifically, can self-selection bias be discounted in this study?

It is encouraging to see that such studies into this question are being staged. Here is the abstract from a study presented 2009 Infectious Diseases Society of America titled, Evaluation of Immunization Rates and Safety Among Children with Inborn Errors of Metabolism.


Background: Children with metabolic disorders are a potential high-risk group for vaccine-preventable diseases. Despite recommendations that they receive all routine immunizations, information regarding both immunization rates and safety data within this population is lacking.
Methods: Using Northern California Kaiser Permanente’s (NCKP) integrated electronic medical record, we identified children up to age 18 years who had an inborn error of metabolism (IEM) from 1990 to 2007. We assessed immunization rates among a subset of infants with IEM born at NCKP who were members until age 3 years matched to healthy infants (1:20), comparing both immunizations received by age 2 years and timing for receipt of vaccines. We next separately assessed for adverse events after immunization by using self-controlled analyses among all children up to age 18 years with an IEM who received at least 1 vaccine at any time, comparing emergency room visits and hospitalizations during post-vaccine days 0-30 to post-vaccine days 31-60.
Results: We identified 79 infants with IEM who were born and remained a member of NCKP at age 3 years. Compared to 1580 matched controls, there was no difference in the proportion of children with IEM up to date for vaccines at 2 years, nor was there any delayed receipt of recommended vaccines during the first year. We also preliminarily identified 322 children with IEM who received any vaccine. Preliminary analysis in this group did not detect an increase in emergency room visits [rate ratio (RR) 0.83, 95% confidence interval (CI) 0.60, 1.14] or hospitalizations (RR 1.1, 95% CI 0.9, 1.4) during the 30 days after vaccination compared to post-vaccine days 31-60.
Conclusion: Children with metabolic diseases in this cohort were vaccinated at rates comparable to healthy children. Although sample size is a limitation, preliminary evidence does not suggest an association between vaccination and an increased risk for serious adverse events.

Emphasis added.

A news story on the subject quoted the session chair where the study was presented:

“These findings are very reassuring,” said Larry Pickering, MD, National Immunization Program, Centers for Disease Control and Prevention, and Emory University, Atlanta, Georgia, who moderated the session at which the study was presented.

“Most of us who take care of kids with inborn errors of metabolism think vaccination is one of the best interventions we can offer them,” he said. “They are at increased risk for devastating complications, even death, from the diseases that the vaccines prevent.”

This is reassuring. Preliminary, yes. I can already see the criticisms, both legitimate and otherwise, that will be levied against this study. but potentially very reassuring. Vaccines are one of the front line interventions in protecting people with mitochondrial disorders.

Let’s see if I can predict the criticisms:

1) not peer reviewed
2) many authors received grant money from vaccine manufacturers.
3) the sample size is small (79 infants)
4) the number of infants with mitochondrial disorders is even smaller (7)
5) it would be good to see a comparison of hospitalizations in the months previous to immunizations (if possible)
6) the time spanned by the study covers a large change in the immunization schedule. The sample size of infants immunized in the current schedule is likely to be rather small.

The sample size is small, but it would be interesting to see if the prevalence of metabolic disorders has increased over this time span. But, as autism has shown us, the correlation=causation arguments can be shaky at best.

12 Responses to “Evaluation of Immunization Rates and Safety Among Children with Inborn Errors of Metabolism”

  1. daedalus2u November 2, 2009 at 04:21 #

    I think we would expect to see higher incidences of adverse reactions to vaccines in children with IEM. Having an IEM is going to make just about everything worse. This is not a reason to not vaccinate, it is a reason to be more vigilent about vaccination. A vaccine preventable disease that might be an annoyance for someone without an IEM might be fatal for someone with an IEM. You can’t know “for sure” until you do the studies.

    If herd immunity was sufficiently high, you might consider not vaccinating for some things. With herd immunity teetering on the edge, that is a very risky strategy for someone with an IEM.

    The only expected reason why IEM’s might increase is because they don’t die early because of better disgnosis and health care. For the most part they are genetic diseases due to the loss of specific enzymes.

  2. hera November 2, 2009 at 17:52 #

    Maybe I am missing something here, but it seems that the only adverse event being checked for is increased hospitalizations in the first month when compared to the second month after vaccination?
    Given that you mentioned Hannah Polings’ case, I expected some kind of neurological tracking; but autism/speech delay etc are not typically diagnosed in the emergency room.
    Or typically within 30 or even 60 days of onset.

    As you say, it would have been interesting to know what the hospitalization rate was prior to vaccinations being given.

    Out of interest, would you consider the lack of neurological or other chronic diagnosis tracking to be a legitimate critism or not? Would be interested to hear your opinion either way.

  3. passionlessDrone November 2, 2009 at 18:24 #

    Hello friends –

    My thoughts are in some ways similar to Hera’s. For example, I do not believe that Hannah Poling was ever hospitalized / or taken to the ER post vaccination. Perhaps I’m wrong on this?

    But the larger issue is that we are using very awkward tools to measure for what could be subtle, but still meaningful changes. For example, the acetaminophen to asthma connection that was only discovered after literally decades of over the counter use in infants. It seems likely that way that tylenol was ascertained to be safe for infants was similarly measured.

    Nice write up. Thank you Sullivan.

    – pD

  4. Joseph November 2, 2009 at 18:55 #

    It’s good to see science doing its thing. First you have non-controlled studies, like the studies that try to find the prevalence of mitochondrial dysfunction in autistics; even though we don’t have a comparable study that uses the same methodology with non-autistics.

    The next step up is case-control studies with matching of cases and controls, hopefully with blinded objective assessments and so forth, and it looks like we’re starting to see these.

    It’s not uncommon that effects that appeared plausible at first no longer show up in the better quality studies.

    Hera’s and pD’s objections are relevant, and you should trust that better science will try to address them, but it’s important to consider that mitochondrial disorder is not just about autistic-like regression. Symptoms include loss of muscle coordination, heart disease, kidney disease, severe constipation, respiratory disorders, seizures, visual or hearing problems, etc. If vaccination is a significant trigger, should you see significant hospitalizations as a result? I would think so.

  5. Tom November 3, 2009 at 19:34 #

    Conversely, a recent study of kids w/mito disorders in Ireland finds a hospitilization rate of 5% for varicella infection vs. .01% in normal kids. All these hospitalizations were due to metabolic decompensation, not secondary bacterial skin infections.
    The Irish group recommends varicella vaccination (a live virus) for mito kids except possibly for those with significant immunosuppression. http://adc.bmj.com/cgi/rapidpdf/adc.2008.147934v1

  6. Sullivan November 3, 2009 at 20:42 #


    interesting paper.

    I find it, well ironic is a polite term, that the vaccine skeptics can dismiss diseases like varicella as no big deal. These same groups claim to represent children who are vulnerable to toxins.

    Here is a clear example of a group of people who are vulnerable to diseases. What is so difficult about the idea that vaccinating the rest of us protects this vulnerable segment?

  7. Tom November 3, 2009 at 21:08 #

    Hi Sullivan,

    The anti-vax position on mito is soooo convoluted. They dearly want to believe that this sub group proves the link between autism and vaccines and yet mito specialists recommend vaccination. If they had it their way, anti-vaxers would deny mito kids the vaccines that save them from horrible morbidities and the very real possibility of death.

    That John Poling can’t or won’t see the light goes to show that when it comes to your own child even a clinician’s judgment can be severely impaired.

  8. dr treg November 3, 2009 at 23:59 #

    Isnt it time the term “inborn errors of metabolism” is abandoned for identified genetic diseases.
    Some of these identified genetic diseases such as PKU, mitochondrial diseases and SHANK3 etc; mutations are associated with autistic behaviour.
    The question should be:
    “Do any immunisations cause the unveiling or deterioration of genetic diseases associated with autistic behaviour”
    which is unlikely to be answered for certain using the scientific method because of lack of funding.

  9. daedalus2u November 4, 2009 at 13:55 #

    No Dr Treg, the question should be “in an individual with IEM, do the risks of vaccination (likely greater in those with IEM) outweigh the benefits of vaccination in preventing the adverse effects of vaccine preventable diseases (which are definitely much worse in those with IEM)”.

    It makes no sense to look at only the adverse effects of vaccinations on those with IEM without looking at the benefits in preventing the disease which is going to be worse in those with IEMs.

    If vaccinations cause the “unveiling” of autism-like symptoms, getting the disease that the vaccine prevents would undoubtedly be many times worse. There is nothing special about vaccinations as immune system stimulations compared to actual diseases other than that the vaccination is milder and has been demonstrated to be much safer in normal individuals than the disease.


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