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Maternal Tdap vaccination during pregnancy is not associated with autism in the child

In this edition of antivaccine Whac-A-Mole, Orac discusses a large study that fails to find a link between maternal Tdap vaccination and autism in the baby. No big surprise there. So, mothers, get your Tdap to protect your baby.

If there’s one idée fixe among antivaxers (besides the long disproven ideas that vaccine cause autism and a large number of bad health consequences, or, as I like to call it, “It’s always the vaccines—always”), it’s utter horror that the CDC and medical profession would recommend that pregnant women be vaccinated against certain diseases. For instance, antivaccine ideologues are utterly convinced that the flu vaccine, when administered to pregnant women, causes miscarriages when it does not and in fact, one outlier study to the contrary, the overwhelming preponderance of evidence supports the conclusion that vaccinating pregnant women against the flu vaccine is safe and effective and protects a vulnerable population (pregnant women) from the adverse consequences of the flu. In fact, if anything, vaccinating against influenza during pregnancy is associated with lower rates of stillbirth, neonatal death, and premature delivery as well as lower risk of the flu in the infant. Of course, antivaxers hate the CDC recommendation to vaccinate pregnant women against pertussis using the Tdap combination vaccine. It’s already been shown that doing so is safe in terms of not increasing the risk of stillbirth, premature delivery, maternal or neonatal death, pre-eclampsia or eclampsia, haemorrhage, fetal distress, uterine rupture, placenta or vasa praevia, caesarean delivery, low birth weight, or neonatal renal failure. But what about autism? Well, thanks to a new study, we have good evidence that maternal Tdap vaccination during pregnancy doesn’t increase the risk of autism in the baby either.

The evidence comes in the form of a study published earlier this week in Pediatrics from a group based at Kaiser Permanente Southern California led by Tracy Becerra-Culqui, which provides robust evidence that vaccinating the mother during pregnancy does not place the baby at a higher risk for autism.

The Tdap vaccine, of course, contains vaccines against tetanus, diphtheria and pertussis, the last of which causes whooping cough. In order to protect the mother and baby, the Centers for Disease Control and Prevention, the American College of Obstetricians and Gynecologists, and the American College of Nurse-Midwives all encourage expectant mothers to get the Tdap vaccine in the third trimester of pregnancy to protect their babies from pertussis.

The authors summarize the rationale in the introduction:

Prenatal tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis, adsorbed (Tdap) vaccination has been shown to be effective in protecting vulnerable young infants from pertussis. Prompted by waning immunity, pertussis incidence has risen in the past decade in the United States, with peaks in 2010 and 2014.1,2 Young infants are at the highest risk of hospitalization and death after pertussis infection, a highly contagious respiratory disease (whooping cough) caused by the bacterium Bordetella pertussis.3 In response, in October 2011 the Advisory Committee on Immunization Practices (ACIP) recommended that unvaccinated pregnant women receive the Tdap vaccine after 20 weeks’ gestation.4 Given the seriousness of the matter, this recommendation was amended in October 2012 to include all pregnant women regardless of previous vaccinations, and the optimal vaccination period was defined between 27 and 36 weeks’ gestation.5 Evidence revealed that antibodies are passed along to newborns, and the vaccine was 91.4% effective in providing some immunity until newborns reach 2 months of age, the age they are expected to receive their first dose of the diphtheria-tetanus-acellular pertussis vaccine.6,7 Given the increasing practice to vaccinate pregnant women with Tdap, it is important to address the concern of a potential link between maternal vaccination and subsequent development of autism spectrum disorder (ASD) in children.

At the risk of sounding as though I’m advocating “suppressing research,” I can’t help but point out right here that this is a study that probably didn’t need to be done, at least not from a strictly scientific basis. There’s no known mechanism and no good preliminary data to suggest that there might be a link between prenatal vaccination with Tdap and the subsequent development of autism. Again, this is a study that was done primarily because antivaxers keep agitating and spreading misinformation that vaccines cause autism rather than from any compelling scientific rationale. I suppose you can justify the study because of the lack of evidence regarding long term effects of Tdap vaccination of pregnant mothers on the risk of autism in their offspring, but mechanistically speaking it’s not a super compelling justification. But, as I say, I’ll allow it.

Now one of the great things about Kaiser Permanente is that it has a unified electronic medical record from which information very useful for doing epidemiological studies can be readily extracted and analyzed. Couple that with a large number of members (over four million), and you have a very nice source to mine looking for correlations between vaccination and adverse outcomes. This particular study was a retrospective cohort study that looked at the outcome of a diagnosis of an autism spectrum disorder in children all Kaiser Permanente Southern California (KPSC) hospitals born between January 1, 2011 and December 31, 2014. The authors note that all recommended immunizations are free to members, regardless of the specific copayment required by the Kaiser plan to which they belong.

Eligibility was restricted to pregnant women who had not undergone in vitro fertilization to get pregnant and who delivered live singleton infants between 22-45 weeks’ gestation. Because of KPSC’s electronic medical record, the children’s medical records were linked longitudinally using unique identifiers. Children with chromosomal or congenital anomalies were excluded. Maternal Tdap vaccination was captured from the EMR and defined as receipt of the vaccine during any point during the pregnancy, and an ASD was defined by a clinical diangosis any time after turning one year of age as recorded in the EMR between January 1, 2012 and June 30, 2017.

Naturally, a number of potentially confounding factors were incorporated into the analysis, such as maternal age, race and/or ethnicity, language, educational attainment, medical center of delivery, type of health insurance, parity, receipt of influenza vaccine during pregnancy, start of prenatal care, and medical complications of pregnancy, such as pregestational hypertension, preeclampsia or eclampsia, pregestational and gestational diabetes, placenta previa, and placental abruption. Children were followed from birth to first ASD diagnosis, end of membership in the health plan, or the end of the study follow-up period, whichever came first. Age of ASD diagnosis, and the incidence rate of ASD diagnosis by Tdap vaccination status were calculated.

Here’s a flowsheet for the study:

Study flow sheet
Study flow sheet

The authors found that Tdap vaccination coverabge ranged from 26% for the 2012 birth cohort to 79% for the 2014 birth cohort, which to me represents a very impressive increase in Tdap coverage over just a three year period. The mean gestational age at vaccination was 28 weeks, and women vaccinated during pregnancy were more likely to be Asian-American or Pacific Islander, have a bachelor’s degree or higher, be nulliparous, have received the influenza vaccine prenatally, and give birth at term (≥37 weeks’ gestation) compared with unvaccinated women.

The raw data showed that 569 children (1.5%) whose mothers received the vaccination were later diagnosed with autism, compared with 772 children (1.8%) whose mothers did not get the shot. Overall, the ASD incidence rate was 3.78 per 1,000 person-years in the group who received the Tdap, while it was 4.05 per 1,000 person-years in the unvaccinated group. The unadjusted hazard ratio was 0.98. After accounting for the various confounders in an analysis known as propensity score weighting, the adjusted hazard ratio was 0.85 (95% confidence interval: 0.77-0.95), which means that the risk of ASD in children of mothers vaccinated with Tdap during pregnancy was actually slightly lower than in the unvaccinated. However, the authors were cautious and simply concluded that their study didn’t provide any evidence of increased risk of ASD associated with prenatal vaccination with Tdap, which is an appropriate way to interpret the data. That doesn’t however, mean that they don’t allude to it in the discussion:

In this large retrospective observational cohort study of 81,993 pairs of diverse pregnant women and their children, we found no evidence of increased risk for ASD diagnosis associated with Tdap vaccination during pregnancy. Subanalyses supported the overall results, revealing minimal variability by year of birth and parity. No study to our knowledge has been published with results examining the risk of ASD after maternal exposure to the Tdap vaccine.

Maternal immune activation during pregnancy is hypothesized to indirectly affect fetal neurodevelopment.32–35 Researchers have found infections during pregnancy (eg, rubella and influenza), including prolonged episodes of fever to increase autism risk, hypothesizing that maternal infections, cytokine responses, and proinflammatory pathways are likely to alter fetal brain development.32,36–41 Our results potentially indicate that the maternal Tdap vaccine affects immune trajectories protecting infants against infections that would otherwise lead to neurodevelopmental alterations.

The study is not perfect, obviously. For one thing, it’s retrospective and thus prone to all the biases and shortcomings to which such studies are inherently prone. However, the authors did a good job controlling for those biases. Another issue was that ASD status was determined by diagnoses recorded in the EMR and was not confirmed by a study-specific standardized assessment. However, they also note that ASD diagnoses were also likely captured consistently during most of the study years because of a California law (Senate Bill 946) that require health plans to cover ASD-related health costs, such as diagnostic and behavioral health treatment, which led to the implementation of systematic procedures for screening and diagnosing within the KPSC health care system. That means that an ASD diagnosis can only be made by a qualified mental health professional. The authors also note that the combined prevalence of ASD in their study was 1.6%, indistinguishable from the 1.7% prevalence reported in the US among eight-year-old children.

There were strengths, as well. One strength is that maternal Tdap vaccination and ASD information were not subject to recall bias, and weighting procedures enabled investigators to balance Tdap exposed and unexposed groups statistically. Also, children whose first ASD diagnosis was before age 2 also had a diagnosis after age 2, which aligns with the American Academy of Pediatrics autism screening recommended schedule of 18- and 24-months.

The bottom line is that, as is the case with every well-designed study of vaccines and autism, this study is yet another negative study. There isn’t even a whiff of a hint of a whisper of a correlation between maternal Tdap vaccination and autism in the mother’s child. Same as it ever was for every other vaccine tested and autism.

By Orac

Orac is the nom de blog of a humble surgeon/scientist who has an ego just big enough to delude himself that someone, somewhere might actually give a rodent's posterior about his copious verbal meanderings, but just barely small enough to admit to himself that few probably will. That surgeon is otherwise known as David Gorski.

That this particular surgeon has chosen his nom de blog based on a rather cranky and arrogant computer shaped like a clear box of blinking lights that he originally encountered when he became a fan of a 35 year old British SF television show whose special effects were renowned for their BBC/Doctor Who-style low budget look, but whose stories nonetheless resulted in some of the best, most innovative science fiction ever televised, should tell you nearly all that you need to know about Orac. (That, and the length of the preceding sentence.)

DISCLAIMER:: The various written meanderings here are the opinions of Orac and Orac alone, written on his own time. They should never be construed as representing the opinions of any other person or entity, especially Orac's cancer center, department of surgery, medical school, or university. Also note that Orac is nonpartisan; he is more than willing to criticize the statements of anyone, regardless of of political leanings, if that anyone advocates pseudoscience or quackery. Finally, medical commentary is not to be construed in any way as medical advice.

To contact Orac: [email protected]

113 replies on “Maternal Tdap vaccination during pregnancy is not associated with autism in the child”

There isn’t even a whiff of a hint of a whisper of a correlation between maternal Tdap vaccination and autism in the mother’s child.

Of course not but failed epidemiologist Jake Crosby has managed to implicate influenza vaccination from this study.

Yeah, I saw that, but the idea was dumb and I’m so resistant to giving The Gnat any attention that I decided not to include a mention of it in this post. 😉

I don’t blame you a bit but I think it’s a good example of the mental contortions an anti-vaxxer performs to rubbish yet another study that doesn’t support them. One can only hope that this resonates with the vaccine-hesitant group and will be widely communicated.

Let’s see about any correlation between autism and vaccinations, because it seems though that the CDC and FDA are hiding any truth on underlying causes of autism spectrum disorder (ASD). According to the CDC 1 of 55 individuals are diagnosed with autism (abroad children). We also know that thousands of parents have indicated when their child received his/her 18-month vaccinations changes occurred soon after, such as fevers, ear infections, slowness in speech and eye contact, repetitive behavior, fixation on objects or subject matters. Now as a professional academic student at a doctorate student, a former educator for the Dept. of Defense Schools, and mother of a 18-year adult son with autism, please explain away why there are thousands of cases of children diagnosed with autism, right after their 18-month scheduled vaccinations? Well my son is one of the thousands of children diagnosed with autism after he received his multiply scheduled vaccinations at 18-months. If, I knew what was known now those vaccinations would of been spaced out, who knows my son could of been a normal, now adult. Please explain away, because thousands of parents will soon be asking the CDC and FDA reports from the past 30-years, and petitioning the Supreme Court for those records.

Now as a professional academic student at a doctorate student, a former educator for the Dept. of Defense Schools, and mother of a 18-year adult son with autism, please explain away why there are thousands of cases of children diagnosed with autism, right after their 18-month scheduled vaccinations?

Your so-called “qualifications” as an appeal to your own “authority” make no sense. If you researched this then you would know that ASDs are typically diagnosed after the age of two although signs are often observed at around 1-2 years when language and social milestones become more pronounced. This coincides with vaccinations given at one year to 18 months. How can you say your son would be “normal” (which is a lousy thing to say by the way) if not for vaccines? Are you a medical intuit? You believe anecdotes and obviously conspiracies so I doubt there is anything that can be said that would resonate with you outside of nurturing your conspiracies.

Does your experience as a “professional academic student at [sic] a doctorate student, a former educator for the Dept. of Defense Schools” include research in developmental biology? If so, you should be able to appreciate the evidence discussed in the references linked below that ASD is expressed early in development because “ASD begins in prenatal and early post-natal life,” since the meme that children with ASD were developing normally until their vaccinations is obviously nonsense.

https://www.ncbi.nlm.nih.gov/pubmed/28803559
https://www.ncbi.nlm.nih.gov/pubmed/29934544

“… a former educator for the Dept. of Defense Schools,…”

Woot. You taught kids in military bases somewhere on this planet. Your students would have been somewhere between kindergarten and high school seniors. As an Army brat at least one of my nine school districts was a DoD school. It is not special, other than young teachers can get experience teaching and living overseas (and in on class we students had to explain to the distraught young teacher that due to the poverty of the area outside of base that cars are often broken into, and that it was wise to leave them unlocked).

“..please explain away why there are thousands of cases of children diagnosed with autism, right after their 18-month scheduled vaccinations..”

Citation needed. It must be PubMed indexed studies by reputable qualified researchers not on the Dwoskin payroll.

It’s being studied. IIRC there’s an association but there are so many other confounding factors: maternal age, maternal health. So it’s really hard to say that IVF has anything specific to do with autism at this point.

IVF also correlates with higher maternal age, a history of complicating factors, and being able to afford IVF. They probably figured that it was better not to compound the compounding factors.

To get a little more mathy, if IVF per se does nothing, but IVF is indicative of age/health/income, then adding IVF means you are counting three things in four ways. Since there’s noise in every variable, what you are doing is decreasing the quality of your data without adding any new information. The new info would be that IVF changes autism risk, even when you compensate for all the other possible variables.

I wish the Tdap vaccination rate for pregnant women where I am was 72%. Based on what I’m seeing it’s around 30-40%. And this year is likely to be a high pertussis outbreak year, too.

Moose:

I notice that Jake has been busily writing his blog for the past month or so. He carries on about vaccines and denigrates an actual journalist** against whom he’s held a grudge for several years. He lists his blog, AoA and Epoch Times as employment on Linked In.

With all the money in his family you’d think that someone would have the presence of mind to either get him counselling or create a make-work job for him at one of their companies.

** like many anti-vaxxers, he constantly insults real journalists and scientists.

Well, if that flu vaccine interpretation is any indication, it’s a good thing that there is a family to feed him because he’d starve if he had to earn a living by his own data analysis skills…

The two key reasons I chose Kaiser for my health coverage are that they’re a bastion of science-based medicine, and they’re a completely integrated service provider.

No risk of being offered homeopathic power-placebos or similar dreck, and no resources wasted on the usual tug-of-war between doctors and insurers.

race and/or ethnicity, language, educational attainment, medical center of delivery, type of health insurance, parity, receipt of influenza vaccine during pregnancy,

Forgive the crazy question from the peanut gallery. What does “parity” mean in this listing?

Great news about Tdap vaccination during pregnancy!

Orac writes,

Same as it ever was for every other vaccine tested and autism.

MJD says,

I’m not convinced, especially in the etiology of allergy-induced regressive autism.

I’m unable to respond with specifics based on Orac’s “gag order” inhibiting MJD from discussing XYZ, and all that it encompasses, at Respectful Insolence.

@ Squirrelelite,

I just love your nym picture showing a squirrel handling an acorn; such a cute fluffy tail!

Q. Do squirrels cherry pick.

Glad you like it! It’s an Abert’s squirrel. They are common in northern New Mexico. If you go picnicking in some the forests, they will compete with the Steller’s Jay’s to steal food off your table.

I sympathize with your problems caring for an adult with autism. I know a lady from our church who has been caring for her adult son for over 20 years. I would guess he has an ASD but don’t really know. She brings him to church and takes him out shopping but he never says much. Having more active behaviors would make it even harder.

But finding some external factor to blame won’t help your son. And research like the meta-analysis I also cited indicates this is a sidetrack at best to finding the real cause(s) of autism and how to help with its many forms.

Do you think that constantly referring to yourself in the third person might be considered to be aberrant, on top of everything else?

Or perhaps this:

https://www.autismspeaks.org/science/science-news/researchers-say-regression-autism-common-variable-maybe-universal

the consensus at the workshop was that regression may represent a near-universal aspect of autism that can affect far more developmental skills than just speech. New research, for example, suggests that regression in babies can take the form of subtle losses in motor skills and attention to social cues. Parents and doctors are less likely to notice these early signs of autistic regression than they are the loss of language and sociability seen when regression takes place in toddlers who’ve already begun talking.

Or perhaps this:

ASD behavior was present early in fine-grained behavioral coding regardless of whether the child was detected early or later by diagnostic tools. This early developmental presence of ASD is expected because abundant new postmortem, cellular, molecular, genetic, and animal model evidence shows that autism is a prenatal neural disorder.

https://www.ncbi.nlm.nih.gov/pubmed/28803559

Fine-grained behavioral coding?

MJD says,

Fancy wording for sure. They’re enlightening and comforting; like eating a bowl of ancient grains. I’ve described in great detail the biological mechanism-of-action that clearly differentiates early onset autism from late onset autism.

@ Orac,

This is a great teaching opportunity for newbies…may I?

I’ve described in great detail the biological mechanism-of-action that clearly differentiates early onset autism from late onset autism.

(Sigh)

I agree with this study and Orac’s writeup about it. Except for one thing: there IS a proposed mechanism for how vaccination in pregnancy could cause autism: via immune activation. The study was a good idea and well worth the effort.

I do think the study is evidence that a single dose of TDaP given during pregnancy does not increase autism risk.

However!

1) Its a single dose of a vaccine. Thats not enough of an immune activation to impact the fetus. By comparison, infants receive

2) Transport of Al adjuvant particles is driven by inflammation, and inflammation is inhibited during pregnancy. Therefore, it makes sense that Al adjuvant will have less transport during pregnancy, and therefore be less damaging.

3) Transport of Al adjuvanat across the placenta is probably low. There is no data on this to my knowledge, but I have looked at papers on nanoparticle transport across the placenta. Sometimes nanoparticles can cross the placenta, and sometimes not. Al adjuvants are phagocytosed and transported by macrophages, and so are not freely floating around in the blood. It appears that maternal macrophages do not cross the placenta, and so cannot carry Al adjuvant particles into the fetus.

The experimental work with NPs is often done by IV or intraperitoneal injection of NPs. These experiments are likely not relevant to Al adjuvant.

Smaller particles in general have greater transport across the placenta, presi=umably by diffusion. Though Al adjuvants are nanoparticulate, they are agglomerated (stuck together to form larger particles) and inside macrophages. This implies that Al adjuvants cannot cross the placenta by diffusion.

4) TDaP is given sometime late in pregnancy, perhaps in the 3rd trimester. This does not leave much time for Al adjuvant particles to travel into the fetus, assuming thats even possible. Al adjuvant transport happens slowly. it takes months.

I think these factors explain why no autism effect occurred, even if Al adjuvanted vaccines cause autism (and other injuries) when injected into infants.

I do NOT think the study is relevant to the safety of vaccines given to infants. And of course that should be the main issue.

…even if Al adjuvanted vaccines cause autism (and other injuries) when injected into infants.

“If”, as the Spartans replied to Phillip the 2nd of Macedonia.
If you want us to accept your hypothesis, bring the evidence. And by “evidence” I mean large, well-designed studies that support it.

Look, Dan, everybody knows that you’re stinking up the joint because nobody gives a shit about you or your blog piracy site. The problem with this approach is that nobody really gives a shit about you here, either.

VP: “I intended to say “Infants receive 17 aluminum-containing vaccines in the first two years.”

Then you intended to say something demonstrably false. Infants are recommended to get a grand total of 5 vaccines containing aluminum adjuvant in the first two years.

https://www.cdc.gov/vaccines/schedules/downloads/child/0-18yrs-child-combined-schedule.pdf

The only way you could get to 17 is by counting total doses. It’s like telling someone with a serious infection whose doctor prescribed a twice-a-day antibiotic pill to be taken for two weeks “Omigod! Your doctor is giving you 28 antibiotics!!!”

That tactic (commonplace with antivaxers) can only be viewed as a mark of stupidity or willingness to engage in deception.

When it comes to Al adjuvant toxicity, its the number of doses that is important because this is what determines the exposure to Al adjuvant.

Your argument requires, for example, that Al adjuvant from 1 dose of DTP or 4 doses of DTP would present the same risk, which makes no logical sense whatsoever.

Don’t you get it? Vaccines, including their antigens as well as all ingredients, including preservatives, adjuvants, excipients, etc, are all perfectly safe, no safety issues whatsoever, no risk. They are all like a saline placebo. So of course 4 doses of DTaP would be just as safe as 1 dose of DTaP.

It will never cease to amaze me just how incredibly nitpicky The Orac and all his minions can be with any study suggesting any sort of safety concern with any vaccine. Seriously, you guys will wax poetic for a thousand words about a small sample size in a pilot study. But then take a study like the one discussed here, which finds no safety concern with a vaccine, and you all suddenly become uncritical unthinking automatons, parroting messages of vaccine safety and efficacy with zero attention to detail.

What gives?

Care to provide critique for the following article? See if you can actually stick to content of the article. There are multiple fatal flaws with this study which you fail to consider.

Study Claims Tdap Vaccine in Pregnancy Doesn’t Cause Autism—Is That True Given The Facts?
https://worldmercuryproject.org/news/study-claims-tdap-vaccine-in-pregnancy-doesnt-cause-autism-is-that-true-given-the-facts/

What about this analysis?

Influenza Vaccination During Pregnancy: A Critical Assessment of the Recommendations of the Advisory Committee on Immunization Practices (ACIP)
Ayoub and Yazbak
http://www.jpands.org/vol11no2/ayoub.pdf

That’s because the study that found an autism risk with flu vaccination in pregnant women was an outlier. That is, it didn’t agree with the rest of the research that found no risk.

That is a red flag for a methodological flaw, and one was found as Orac discussed.

Small sample sizes isn’t always bad in science as long as you acknowledge the limitation and control for its effects. The studies that you like seldom if ever do that.

Your a citations are a joke. I don’t have time for an indepth analysis of all the flaws (it’s late and I have work in the morning) but a quick glance found several in your first citation:

Package inserts are legal documents. They are of little value in establishing risk.
Few medications have been evaluated for pregnant women because of ethical concerns with using pregnant women as human subjects. Flu vaccines are have been, and have been found safe, and to reduce risk of pneumonia as a complication of flu, which is dangerous for mom and baby.
Even meds that haven’t been tested (are pregnancy category B or C for example) are routinely given to pregnant women because the benefits outweight the known risks which are few.
Who funds a study isn’t always an indication that the study is bad as long as it is disclosed. Kaiser Permanente has a vested interest in keeping women and babies healthy; they are not in the business of taking risks that will create life long health problems that they have to pay for. So that they paid for a flu vaccine study in pregnant women is not a red flag that some mysterious force is distorting the science. Far from it; if there were really a problem, they’d be at the forefront of critics for flu vaccination in pregnant women. They’re not. Nice try, but fail.

Even meds that haven’t been tested (are pregnancy category B or C

Next to nothing is category A. I thought the system was due for overhaul, but I haven’t followed it.

It’s hard to take you seriously. So if a study reaches a different conclusion than previous studies, that in itself is a “red flag for a methodological flaw”? Really?

I thought it was obvious that my comment about sample size was sarcasm directed at those who frequent this site as they have a penchant for criticizing studies for issues which are irrelevant given the studies’ design and intent (like criticizing a pilot study for having a small sample size, or criticizing a case series analysis of a new condition for not having a control group).

Your explanation for why these vaccines have not been tested in pregnant women is ridiculous. Researchers test infants all the time, so why would there be ethical concerns about using pregnant women to test safety and efficacy of vaccines which you intent to recommend, universally, to pregnant women? In a more perfect world any such recommendation would require safety data using the same population they intend to recommend the vaccine or drug for.

It is interesting that you choose not to address the content of an article which provides numerous explicit and well-reasoned criticisms of the study being exalted here. Some of these criticisms are for fatal flaws which would lead The Orac or any of his minions to immediately pillory any study if it was in any way critical of vaccines. So again I ask, what gives?

Any comments about the paper by Ayoub and Yazbak? I understand you think these people are walking Anti-Christs, but do you have anything to say about their actual arguments? I direct you specifically to the section “Is Influenza Vaccination Safe During Pregnancy?”.

Obviously you do not understand when I request papers only from reputable qualified researchers. There is a reason we do not respect those who work to get those who murdered babies by shaking off the hook by blaming vaccines.

So what is happening these days with their “poster boy” Alan Yurko? Your “heroes” got him off the hook after he murdered his girlfriend’s baby: http://www.ratbags.com/rsoles/comment/yurko1.htm

Where is he these days?

So if a study reaches a different conclusion than previous studies, that in itself is a “red flag for a methodological flaw”? Really?

Yes. It’s simple odds. What’s more likely? That one study that contradicts the results of several prior studies is flawed or an outlier, or the several prior studies are flawed?

It will never cease to amaze me just how incredibly nitpicky The Orac and all his minions can be with any study suggesting any sort of safety concern with any vaccine.

If “nitpicky” puts your idiot panties into a fucking twist, there’s always bluntness.

Bueller?

Anyone care to respond to the seven criticisms leveled against this paper by the World Mercury Project?

No. Why should I give a crank organization such as the World Mercury Project the time of day?

Translation of Chris’s response below: “Damn, those criticisms look valid…time to pull a red herring out of my butt.”

Actual translation of Chris’s response: “The World Mercury Project are cranks, their arguments are P.R.A.T.T.s and David Foster won’t believe my rebuttals, so why should I bother?”

Mr. Foster, the criticisms of the World Mercury Project are not valid. Also Robert Kennedy, Jr is a crank.

The only one that seems to me to be a valid is the claim about the age of the groups, and even that’s a problematic claim. I’d be happy to hear from people with more expertise about whether any of my comments are wrong.

The first flaw is not a flaw. The study used the minimum age for diagnosis – not a maximum. Using minimum age doesn’t prevent identifying later cases, so it reads as if Hooker misunderstood. He is saying they should have used a later age, but that diagnosis is done later. It seems like an error to me.

The second point is also wrong. The children not enrolled with Kaiser for more than 3 months were not counted as controlled, they were dropped from the study and not counted, simply since they were not in the system long enough to check for autism. “After excluding an additional 9356 (8.5%) children with <90 days of continuous enrollment and 3051 (2.8%) diagnosed with chromosomal or congenital anomalies, the study included 81 993 children (Fig 1).”

The third point is correct insofar that the mean differed, but it’s not clear why that’s a fatal flaw: the age range of the groups was similar, and in the study, too, most diagnoses were at a younger age – in both group. It’s a real and addressed difference, but I’m not clear why Hooker thinks it’s meaningful. After all, the diagnoses rates among the older group 5-6 – were similar across groups. He gives no link or source for why he thinks it’s critical. The age was determined by “Children were followed from birth to first ASD diagnosis, end of membership in the health plan, or the end of the study follow-up period (June 30, 2017), whichever came first.” It’s not clear why this approach is not valid, and the results it yielded not, either.

The fourth is not a flaw either. What is the basis for including vaccination status of the child when you’re looking at the effect of Tdap? Basically, these comments suggests either misreading of the study or they’re not actually flaws.

The fifth is not a flaw either. Using person years is not unusual in vaccine studies, and as long as it’s done for both groups, groups with similar age distribution, isn’t an issue.

Authors getting a fund for a different study doesn’t nullify the study. It’s a pretty weak conflict of interest, too.

Kaiser funding isn’t a flaw, either.

Again, I’m happy to hear if this is incorrect.

Also from the WorldMercuryProject article I mentioned already, does it bother anyone here that neither of the two vaccines being given to pregnant women have even been tested for safety in, um, pregnant women?

According to the manufacturer’s package insert for each, safety and effectiveness have not been established in pregnancy women:

Adacel Safety and effectiveness of Adacel vaccine have not been established in pregnant women. Pregnancy Surveillance Registry: contact Sanofi Pasteur Inc. at 1-800-822-2463 (1-800-VACCINE).

Boostrix Safety and effectiveness of BOOSTRIX have not been established in pregnant women. Register women who receive BOOSTRIX while pregnant in the pregnancy registry by calling 1-888-452-9622.

Pregnant women may participate in clinical research where the “purpose of the activity is to meet the health needs of the mother” regardless of the degree of risk to the fetus and offspring. If the purpose of the research is not to meet her health needs, she may participate only if “the risk to the fetus is minimal.”

Clearly you didn’t bother reading the article did you David Foster?

Chris Preston, you are overestimating Mr. Foster’s reading comprehension. He reads the words, but the meaning eludes him

Chris, David Foster has a cargo cult approach to science. If there are some words in there that he likes the sound of, he assumes it supports his conspiracy theory of the moment without perusing any more.

“Pregnant women may participate in clinical research where the ‘purpose of the activity is to meet the health needs of the mother’ regardless of the degree of risk to the fetus and offspring. If the purpose of the research is not to meet her health needs, she may participate only if ‘the risk to the fetus is minimal.'”

So one of the criteria is “if the risk to the fetus is minimal”, right?

So tell me this. If the CDC has recommended Tdap vaccination to all pregnant women, haven’t they already decided that the “risk to the fetus is minimal”? The answer is either yes or no, and at this point you are not in a very good position regardless how you choose to answer.

The two choices lead to these possible conclusions: (1) your argument is unfounded; or (2) the CDC is recommending the vaccination of pregnant women with a vaccine which they have not determined to be safe for the fetus.

I know I am wasting my time here, but for the potential benefit of others. You cannot go around conducting trials on pregnant women willy nilly.

Tdap has already been shown to be safe to pregnant women and their subsequent babies. It is not necessary to conduct the same studies on every single brand of vaccine when there is no reason to suspect there will be a different outcome (i.e. the other brands have been shown to be safe in other population groups).

So tell me this. If the CDC has recommended Tdap vaccination to all pregnant women, haven’t they already decided that the “risk to the fetus is minimal”?

Well, yes–except that it wasn’t the CDC that decided this but the experts, federal agency representatives and community representative of the Advisory Committee on Immunization Practices (ACIP) who concluded that the safety of TDaP in pregnancy was well established.

Note that the ACIP reported:

In prelicensure evaluations, the safety of administering a booster dose of Tdap to pregnant women was not studied. Because information on use of Tdap in pregnant women was lacking, both manufacturers of Tdap established pregnancy registries to collect information and pregnancy outcomes from pregnant women vaccinated with Tdap. Data on the safety of administering Tdap to pregnant women are now available. ACIP reviewed published and unpublished data from VAERS, Sanofi Pasteur (Adacel) and GlaxoSmithKline (Boostrix) pregnancy registries, and small studies. ACIP concluded that available data from these studies did not suggest any elevated frequency or unusual patterns of adverse events in pregnant women who received Tdap and that the few serious adverse events reported were unlikely to have been caused by the vaccine. Both tetanus and diphtheria toxoids (Td) and tetanus toxoid vaccines have been used extensively in pregnant women worldwide to prevent neonatal tetanus. Tetanus- and diphtheria-toxoid containing vaccines administered during pregnancy have not been shown to be teratogenic.

You might want to consider the (high-dose) preclinical toxicology studies which, like the post-marketing data collected from pregnancies, fail to suggest harm, in addition to reading the reports of prospective studies of the safety of TDaP administration in pregnancy like the example linked below, and see also a review the safety of TDaP exposure on fetuses and infants.

https://bmjopen.bmj.com/content/6/4/e010911.long
https://www.ncbi.nlm.nih.gov/pubmed/28178054

at this point you are not in a very good position regardless how you choose to answer

So you’re down with infantile pertussis? Good to know.

Ha, so brian is citing published journal articles and not his own website comments and letters to the editor?

Major fail.

I’d like to respond to Dorit’s response to the analysis of this study from the World Mercury Project. First, I would like to thank Dorit for at least taking the time to read and respond to the criticisms of this study. I will respond to each comment separately.

First, here are the relevant links followed by Dorit’s comment, followed by my responses.

Hooker’s debunking of tdap/pregnancy safety study:
https://worldmercuryproject.org/news/study-claims-tdap-vaccine-in-pregnancy-doesnt-cause-autism-is-that-true-given-the-facts/

Dorit’s comment:
https://respectfulinsolence.com/2018/08/15/maternal-tdap-vaccination-during-pregnancy-autism/#comment-399314

“The only one that seems to me to be a valid is the claim about the age of the groups, and even that’s a problematic claim. I’d be happy to hear from people with more expertise about whether any of my comments are wrong.

The first flaw is not a flaw. The study used the minimum age for diagnosis – not a maximum. Using minimum age doesn’t prevent identifying later cases, so it reads as if Hooker misunderstood. He is saying they should have used a later age, but that diagnosis is done later. It seems like an error to me.

The second point is also wrong. The children not enrolled with Kaiser for more than 3 months were not counted as controlled, they were dropped from the study and not counted, simply since they were not in the system long enough to check for autism. “After excluding an additional 9356 (8.5%) children with <90 days of continuous enrollment and 3051 (2.8%) diagnosed with chromosomal or congenital anomalies, the study included 81 993 children (Fig 1).”

The third point is correct insofar that the mean differed, but it’s not clear why that’s a fatal flaw: the age range of the groups was similar, and in the study, too, most diagnoses were at a younger age – in both group. It’s a real and addressed difference, but I’m not clear why Hooker thinks it’s meaningful. After all, the diagnoses rates among the older group 5-6 – were similar across groups. He gives no link or source for why he thinks it’s critical. The age was determined by “Children were followed from birth to first ASD diagnosis, end of membership in the health plan, or the end of the study follow-up period (June 30, 2017), whichever came first.” It’s not clear why this approach is not valid, and the results it yielded not, either.

The fourth is not a flaw either. What is the basis for including vaccination status of the child when you’re looking at the effect of Tdap? Basically, these comments suggests either misreading of the study or they’re not actually flaws.

The fifth is not a flaw either. Using person years is not unusual in vaccine studies, and as long as it’s done for both groups, groups with similar age distribution, isn’t an issue.

Authors getting a fund for a different study doesn’t nullify the study. It’s a pretty weak conflict of interest, too.

Kaiser funding isn’t a flaw, either.

Again, I’m happy to hear if this is incorrect.”

#1

I can see why you would see this as an invalid criticism, as the WMP article does not explain themselves clearly. The criticism here is not about age of diagnosis per se, they were not suggesting some sort of maximum age of diagnosis or the like. They were criticizing the short length of followup for many subjects, and the fact that the length of this followup was limited by the overall study followup period ending in 2017, with subjects being enrolled as last as 2014. But I agree that the way this is explained is not correct. What they should have said is that with the enrollment period ending in 2014 but the followup period for all subjects ending in 2017, many subjects would have been enrolled at a time when their ASD diagnosis would have been missed by this study, since by 2017 they would still be younger than the average age of diagnosis for ASD. Hopefully this clears up your confusion.

This is a FATAL FLAW for this study.

#2

For #2 again the author does not word his criticism at all clearly, but honestly if you just spend some time thinking about this, you should come to the same conclusion. Instead it is clear you simply chose to see what you wanted to see. So think about it. If a child is in network for only 92 days after their first birthday, s/he meets eligibility requirements correct? But what happens if he receives an ASD diagnosis a year later? He became autistic, and likely did so within even the relatively short follow up times for this study. But in this study he would be counted as a non-autistic control since he was out of network and no longer being tracked in their records. This is not rocket science Dorit.

This is another FATAL FLAW for this study.

#3

If you cannot understand why this is a FATAL FLAW for this study then I cannot help you. Seriously, it’s not just that the mean length of followup is different, it’s that the vaccinated group had 6 months LESS of followup, and the fact that this falls precisely at the average age of diagnosis. Just because the paper addresses this difference does not mean that it does not invalidate the findings. The fundamental root of this problem lies in how this study is structured, with an enrollment period ending in 2014 but then an enforced end of followup occurring just 3 years later. Given that the average age of diagnosis of ASD is almost 4, this completely invalidates these findings.

#4

Your point about this criticism is only valid if you assume a priori that there is no relationship between infant vaccination and autism. Do you really intend to assume that, when the study you are critiquing is looking into a possible connection between…wait for it…vaccination and autism? That is patently absurd. Why NOT include vaccination status of the infant, if for nothing else simply to be able to discount it as a possible confounder?

#5

In your analysis for this criticism, you state that it is acceptable to use person-years so long as the age distributions are the same for both groups. But go back to criticism #3, where the average length of followup is different between the vaccinated and unvaccinated groups. This means that these groups are not evenly distributed across the time range of this study. There are many many examples of vaccine safety studies inappropriately using person-years in order to confound the results.

#6

Receiving funding from the manufacturer of the vaccine you are studying for safety is not a conflict of interest? That is the very definition of a conflict of interest. It does not invalidate the results, but should call for greater scrutity, especially since this is now the second study funded by the manufacturer.

#7

The claim was not that the funding by Kaiser was itself a problem, the problem here is that the data set is not available, therefore this study cannot be replicated, and its conclusions cannot be validated.

I find it interesting that you chose not to address the following:

“Note that in a pull-out section, “What This Study Adds,” the journal states: “No study to our knowledge has been published examining the risk of ASD after prenatal exposure to the Tdap vaccine.” WMP believes that this is a startling admission pointing to our poor vaccine safety program in America and wonders given the clear links of Maternal Immune Activation (MIA) and autism why there wasn’t a study done BEFORE the recommendation to begin giving this vaccine to pregnant women?”

“Hooker’s debunking…”

Hooker is neither a qualified nor reputable researcher.

Mr. Foster, what is your education and relevant experience?

So let me make sure I have this right. Orac’s entire blog is exalting a study which he claims provides evidence that it is safe to give tdap vaccine to pregnant women. I post an article which calls out 7 specific criticisms of this study. The only person here who even attempts to address those criticisms is Law Professor Dorit Reiss, although not a very good attempt but at least she gave it a try.

But instead of actually addressing any of the criticisms, and trying to defend this very flawed study, all you can do is:
1) Question Hooker’s credentials.
2) Question my own credentials.

For Hooker you can see for yourself whether or not you think he is qualified to analyze a study like this:
https://www.focusforhealth.org/meet-dr-brian-hooker/

What I find interesting is that you won’t listen to a career-long biochemist but you will agree with everything said by a surgical oncologist and a law professor.

As for my credentials, I have never tried to misrepresent myself, I’ve always been open about the fact that I have no medical training whatsoever. I am a Systems and Site Reliability Engineer (basically a computer geek). But I do have a BS in mathematics with emphasis on probability and statistical methods and a BS in psychology with emphasis on experimental design, so I do know how to interpret a study and I know my statistics. Fair enough?

I don’t really give a flying f*ck whether or not you think I’m qualified to analyze this study, but I would like to know what you think about each of the criticisms leveled, including Dorit’s and my responses.

So far I see absolutely no indication that you even understand what we are talking about.

More about Hooker:

Hooker Vaccine Court lawyer fee ruling, with special words for Shoemaker: https://ecf.cofc.uscourts.gov/cgi-bin/show_public_doc?2002vv0472-132-0

Final Hooker ruling: https://ecf.cofc.uscourts.gov/cgi-bin/show_public_doc?2002vv0472-118-0

So you took engineering statistics, so did I. Then later I took general statistics and found out about all the stuff they skipped, especially the stuff on ethics and sampling bias when using human subjects. Apparently that was not important for engineering, because light bulbs and widgets are not covered by the Belmont Report.

By the way, Hooker is a chemical engineer, so he has the same lack of education.

Also, I don’t think Hooker’s opinions are worth my time. He has an agenda, just like you. His goofy twists and turns on his retracted paper about the MMR vaccines is proof enough he should be ignored. Though he did prove that it is better to get the vaccines on time.

And that poor black kids can also get autism, even with the MMR vaccine. They got the vaccine later because they were admitted to special ed. preschool through ChildFind.

But I do have a BS in mathematics with emphasis on probability and statistical methods and a BS in psychology with emphasis on experimental design, so I do know how to interpret a study and I know my statistics. Fair enough?

Heh. Explain what measure is without cheating.

Receiving funding from the manufacturer of the vaccine you are studying for safety is not a conflict of interest?

Kaiser Permanente is a Health Insurer, not a vaccine manufacturer. You got a very basic fact wrong, which raises questions about a lot of your arguments.

Well, I would first point out your logical fallacy that unless everything I say is true, nothing I say is true. Very convenient. Used by the pseudo-skeptics often.

But more importantly, there are two separate criticisms here and you are confusing them. There is the criticism that the vaccine manufacturers provided funding directly to the authors of this study, via grants related to this study and a previous study. Then there is the criticism that Kaiser funded this study. Two different things.

Who funds a study is a reason to look at the methodology very closely. It does not make a study flawed in of itself.

If Orac dismissed a study simply because it was funded by antivaxxers he’d have a lot less to write about. Instead he actually explains the flaws in antivax studies to show why they are wrong and as Orac puts it, hilariously so.

You need to criticize a study using something other than funding. And as Chris pointed out, funding from Kaiser is not a reason to question a study. They are an insurer, not a vaccine maker. They don’t have a dog in the fight; they just want to know what the evidence based medicine is because an ounce of prevention is worth a pound of cure.

“And as Chris pointed out, funding from Kaiser is not a reason to question a study. They are an insurer, not a vaccine maker. ”

That was Julian.

By the way, I did think it was hilarious. Obviously who has had to deal with a health insurance company would think they are trying to make money with pharmaceuticals. They typically try to refuse to pay for them if they can.

Most recent experience: I was recently bitten by a dog. So I called the health insurance nurse line and asked what I needed to be worried about. The nurse went over what care I should give the wound, and symptoms to look out for and then recommended I go get a tetanus booster.

When I went to the pharmacy to get a tetanus booster (which turned out to be a Tdap), they had to negotiate with the health insurance company since it was less than ten years, until the insurance person checked their records showing that their nurse recommended it because it was more than five years.

When I went to the pharmacy to get a tetanus booster (which turned out to be a Tdap)

My last two have been Tdap’s, even though the U.S. recommendation is only one for adults, with Td otherwise. I find this odd and also wonder how much Td is generally stocked in clinics and EDs, etc.

^ I now recall a search for TT back when I frequented MDC. But, hey, hydrogen peroxide and you’re all set with that puncture wound.

I think now they just stock Tdap in pharmacies. There is probably no reason to stock Td, and the TT may not even be manufactured anymore. Supply and demand.

I can see why you would see this as an invalid criticism, as the WMP article does not explain themselves clearly.

If Hooker can’t explain himself clearly then maybe he should seek another profession. He pulled the “up to 50% of cases” out of his bum. What you and Hooker miss is that the study cut-off period includes both cohorts. So your “fatal flaw” isn’t even a flaw.

For #2 again the author does not word his criticism at all clearly, but honestly if you just spend some time thinking about this, you should come to the same conclusion.

This isn’t a matter of Hooker explaining this “unclearly”, this is Hooker getting it completely wrong. Hooker states: “If a child who received a diagnosis of autism did not receive it within that time period in network, they would be considered a non-autistic control. ” That is false; they simply weren’t included in the final analysis and nor should they be. You state: “This is not rocket science Dorit.” Funny because it sure seems like rocket science to you and Hooker.

If you cannot understand why this is a FATAL FLAW for this study then I cannot help you.

The shortened follow-up was for the last birth cohort only and most of the cases were diagnosed prior to age four. Given that the rate of ASDs in both cohorts was the same for the previous years, why don’t you explain how one cohort that had a contracted follow-up period happened to have a significantly higher rate of ASD which would have to be the case for this to be a FATAL FLAW™.

Your point about this criticism is only valid if you assume a priori that there is no relationship between infant vaccination and autism.

There isn’t and more importantly what is the study hypothesis? Neither you nor Hooker know experimental design well enough to comment so definitively on it.

There are many many examples of vaccine safety studies inappropriately using person-years in order to confound the results.

There are many many examples of vaccine safety studies inappropriately using person-years in order to confound the results.
No doubt you can cite these “many examples”. Expressing the incidence rate in person-years is actually more sensitive than what Hooker says. He doesn’t know what he’s talking about. If multicollinearity has occurred then he could give some actual examples of the variables that have skewed the results. Using person-years is not an example.

Receiving funding from the manufacturer of the vaccine you are studying for safety is not a conflict of interest?

Oh this is so rich coming from a person who has refused to list his many conflicts of interests in “studies”. These authors list theirs and present the data so find the flaws with the data, but so far Hooker has struck out.

The claim was not that the funding by Kaiser was itself a problem, the problem here is that the data set is not available, therefore this study cannot be replicated, and its conclusions cannot be validated.

Of course it can be validated, just apply to the VSD; the authors are not authorised to release the data they acquired from the VSD. Given Hooker’s previous foray into privileged dataset, it’s no small wonder he tried to do an end run or perhaps he knew he would be turned down and could claim the results could not be replicated. So Prof. Reiss was correct on all points, Hooker and by extension you have failed to establish this study is FATALLY FLAWED™ Maybe you should listen to actual epidemiologists instead of some failed “researcher” with an axe to grind.

Thank you for responding “Science Mom”. My first suggestion would be to carefully read the study before commenting, you will see this theme throughout my response.

Regarding the study’s cut-off period, you seem to claim that the difference in average followup periods between the two cohorts (vaccinated vs unvaccinated moms) does not matter because the same cut-off period includes both cohorts. Your reasoning is flawed. The simple fact is that the distribution of birth years is not evenly distributed between the two cohorts, the authors explain this in one of their replies to a submitted comment. So one group had an average followup period which was significantly longer than the other, and it just so happens that the vaccinated had the shorter followup period. For pregnant moms giving birth in 2014 they would have a followup period of only 3 years, this is significantly shorter than the average age of diagnosis for ASD, meaning it is likely that cases of ASD will be missed. This will certainly bias the results towards the null hypothesis. This is a fatal flaw.

As you state: “Hooker states: ‘If a child who received a diagnosis of autism did not receive it within that time period in network, they would be considered a non-autistic control.’ That is false; they simply weren’t included in the final analysis and nor should they be.”

No. Let me try this again. If a mother-and-child pair are in the study for, say, 92 days after birth (which is long enough to be included according to the study’s criteria), but then they withdraw from Kaiser before the child is diagnosed with ASD, they will be counted as a non-autistic control in the study. Please read the study carefully. The fact that they had to remove 10% of their cases because the children had < 90 days of enrollment makes this all the more relevant.

You claim “The shortened follow-up was for the last birth cohort only and most of the cases were diagnosed prior to age four”. Um, what? The shortened followup applies to any and all birth cohorts, since the children for all cohorts were all followed until 2017 at the latest…this cutoff applied to everyone. Furthermore, according to the authors: “The proportion of children with ASD across birth years revealed a decline from 2.0% to 1.5% in the unvaccinated and 1.8% to 1.2% in the vaccinated group”. Why would the proportion of children with ASD in both groups decline by birth year? Because of the freakin’ artificially introduced cutoff of 2017 that’s why! If this study had included mothers who had given birth between 2009 – 2012 but then followed the children until 2017, they would likely not see this difference. The problem is that: (a) most of the vaccinated mothers came in the later years since vaccination rates were significantly higher (26% in 2012 to 79% in 2014); and (2) this means a signifantly shorter followup period for the vaccinated cohort.

You state:

“Given that the rate of ASDs in both cohorts was the same for the previous years, why don’t you explain how one cohort that had a contracted follow-up period happened to have a significantly higher rate of ASD which would have to be the case for this to be a FATAL FLAW™.”

Again, you are completely missing the point, perhaps you should read the paper and Dorit’s and my comments again? The cohort with the contracted follow-up period may very well have children who received ASD diagnoses after the study cutoff in 2017. Do you get it? That means there could be missed ASD diagnoses which are not captured in the study, and this would be more likely to occur in the vaccinated group since they are the cohort which had the shorter follow-up period.

Regarding the fact that they did not include the childrens’ vaccination status, you completely missed my point. When I said “Your point about this criticism is only valid if you assume a priori that there is no relationship between infant vaccination and autism”, I was stating the obvious, that this assumption would be inappropriate. You simply respond with “There isn’t”. And there you have it in a nutshell folks, scientific integrity according to “Science Mom”.

Your last point about availability of the data-set is patently false, please READ THE STUDY. The data did not come from the VSD (Vaccine Safety Datalink), it was collected from medical records collected by Kaiser. When Hooker asked Kaiser for the data, they told him it was not available.

Are you including Law Prof. Reiss as your example of an “actual epidemiologist”? I soundly debunked each of her points.

Yours were even worse.

Flaw 1: Hooker did not “explain it badly”. It spoke wrongly. He claimed the issue was the use of the minimum age, and that’s just not a flaw. There’s just nothing in that statement that supports the claim that cases were missed at all. Average follow up was not different than Hooker’s 42-48 months – it was 42 for the vaccinated group and 50+ for the unvaccinated if you use the median, higher if you use the mean. In other words, this alleged flaw doesn’t hold. It looks like a misreading. Also note that this median includes the 2014 group, for which follow up would be around 3 years because of end of study – for both groups, pulling the median down.

Flaw 2: Your example is incorrect, since the follow up range was 1.2-6.5, and infants had to be members at least 90 days after they turned 1. And this was applied to both groups. Cases who did not qualify were not part of the study, they were not counted as non-autistic controls. They were excluded. Hooker was mistaken when he counted it as 90 days (I misread him initially, and your example did help with that). Also note that the vast majority of end of follow up was because of the end of the study. Not end of enrollment. To make this a flaw you would have to have a reasonable amount of kids who were terminated a short time after a year – and the first quarter of follow up is at 2.9 for vaccinated and 3.7 for unvaccinated, or much higher, suggesting that the children whose follow up ended at a younger age was pretty low.
Doesn’t hold.

Flaw 3: End of follow up applies to both cohorts in the 2014 groups, and to respond to your point, that means that to claim that’s a flaw you have to assume a more kids who were diagnosed later in the vaccinated group – and Science Mom addressed that. The relationship between the rates for that cohort are not different than the differences in the previous years, so that seems a strange assumption. The numbers are pretty similar, and given the similarity with the other years and the explanation, describing this as a fatal flaw still seems strange.
I think Science Mom addressed it generally.

Flaw 4: Again, there is no point to assume the child’s vaccination status is relevant. Science mom was trying to explain to you that the study was focused on a different issue.

Flaw 5: see Science Mom’s explanation and request for studies (that you did not provide). And to remind you, the person years was applied to both groups. Unclear why you think that makes a difference.

Flaw 6: receiving money in another study is a conflict of interest – which is why it was declared, unlike Hooker’s constant habit to drop his – but it is not a serious one. It can call for close reading – but you still have to actually point to a flaw.

Flaw 7: Hooker is not qualified to analyze the data set, as his past efforts and his misreading of it show.

If you can point to a qualified researcher being denied access, let me know.

Prof. Reiss: “Hooker is not qualified to analyze the data set, as his past efforts and his misreading of it show.”

I would love to know if Mr. Foster read either of the rulings from Hooker’s NVICP case. There seem to be some words directed towards his choice of “expert witness” and previously used arguments.

As an engineer I can truthfully say we are not given the proper tools to do epidemiological studies. Mostly because humans are complex than widgets, or plants (which was Hooker’s field of chemical engineering).

For pregnant moms giving birth in 2014 they would have a followup period of only 3 years, this is significantly shorter than the average age of diagnosis for ASD, meaning it is likely that cases of ASD will be missed. This will certainly bias the results towards the null hypothesis. This is a fatal flaw.

If only you and Hooker actually knew what a “fatal flaw” of a study actually was…oh wait…Hooker should know, he’s committed plenty of them and had studies retracted because of them. The authors addressed this by stratifying by birth year as explained. The 2014 birth cohort had at least 3 years (3.5 years actually) of follow-up. If you bothered to look at Table 3 and see the stratification of ASD diagnoses by year then you would see that the majority of ASD cases were captured before the age of 4. Again while a limitation of the study, the cut-off affected both cohorts and full follow-up for the previous birth cohorts does not indicate differences in ASD incidence between groups. Know what a limitation and a “fatal flaw” are before going off half-cocked.

The fact that they had to remove 10% of their cases because the children had < 90 days of enrollment makes this all the more relevant.

Where are you getting that 10% from? But more to the point, again refer to Table 3 and the unvaccinated cohort had a significantly larger loss of follow up due to terminated enrolment. This actually reduced the ASD incidence rate more in the unvaccinated group than the vaccinated group. Personally, I would have excluded them although does little to affect the outcome. Again a limitation not a “fatal flaw”.

The shortened followup applies to any and all birth cohorts, since the children for all cohorts were all followed until 2017 at the latest…this cutoff applied to everyone.

Your interpretation of that is what is flawed. The earlier birth cohorts were already either a.) diagnosed with an ASD or b.) terminated enrolment. It was only the last cohort which did not have 4 or more years of follow-up and since that vaccinated group was the largest, skewed the follow-up time. The number of ASD cases at 5 or 6 is negligible and again since most cases were captured before four years old and follow-up of the last birth cohort was 3.5 years, your claim is meritless.

That means there could be missed ASD diagnoses which are not captured in the study, and this would be more likely to occur in the vaccinated group since they are the cohort which had the shorter follow-up period.

Of course there were probably cases that were not captured but it was in both groups. Your insistence that the vaccinated group as a whole had a contracted follow-up is not correct. Given the 2011-2013 birth cohorts had ample follow-up time to capture ASD cases and the incidence rate estimated, There is no reason to claim that the 2014 vaccinated birth cohort must have had a significantly higher ASD incidence rate.

Regarding the fact that they did not include the childrens’ vaccination status, you completely missed my point. When I said “Your point about this criticism is only valid if you assume a priori that there is no relationship between infant vaccination and autism”, I was stating the obvious, that this assumption would be inappropriate.

Yet this is exactly what you “assumed” when you said:

“Your point about this criticism is only valid if you assume a priori that there is no relationship between infant vaccination and autism. Do you really intend to assume that, when the study you are critiquing is looking into a possible connection between…wait for it…vaccination and autism? That is patently absurd. Why NOT include vaccination status of the infant, if for nothing else simply to be able to discount it as a possible confounder?”

Hooker stated this as well and that was what Prof. Reiss and I addressed. What is the study hypothesis and can you people please ever stop shifting the goalposts.

Your last point about availability of the data-set is patently false, please READ THE STUDY. The data did not come from the VSD (Vaccine Safety Datalink), it was collected from medical records collected by Kaiser. When Hooker asked Kaiser for the data, they told him it was not available.

Mea culpa Kaiser participates in the VSD but my point still stands; Hooker is free to apply to Kaiser to acquire data for a study. Simply emailing them and asking for their data is, rightfully, not going to yield it. Hooker should know this and the hoops he needs to jump through but it makes a better story if he can lazily email for data instead of applying for it, get turned down and then whine.

Are you including Law Prof. Reiss as your example of an “actual epidemiologist”? I soundly debunked each of her points.

Of course she isn’t an epidemiologist, more importantly, neither is Hooker. I suppose in your strange world you can claim superiority over anyone but that only makes it so in your own strange world and not any where else. I notice you completely dropped your claim of numerous examples of multicollinearity in vaccine studies and Hooker’s glaring COI problem. I cop to what I get wrong.

I would like to draw your attention to three different studies which presume to show that vaccination with tdap during pregnancy is perfectly safe. These studies were referenced by various folks responding to my comments.

This is the “science” y’all believe we should rely on to tell us whether tdap vaccination is safe during pregnancy. This is apparently what you believe qualifies as the “settled science”.

Safety and Immunogenicity of Tetanus Diphtheria and Acellular Pertussis (Tdap) Immunization During Pregnancy in Mothers and Infants
https://jamanetwork.com/journals/jama/fullarticle/1866102

1) This study looked at precisely 48 women. 48.
2) The age-matched comparison group was non-pregnant women who also received tdap vaccine.

The study concluded: “This preliminary assessment did not find an increased risk of adverse events among women who received Tdap vaccine during pregnancy or their infants.” Given that, one could reasonably assume that they used a control group of unvaccinated women.

Safety of Tdap vaccine in pregnant women: an observational study
https://bmjopen.bmj.com/content/6/4/e010911.long

1) This study looked at 793 women, but 28% of them also received influenza vaccine concomitantly.
2) The rate of SAE’s (Serious Adverse Events) was 1 in 26, these included obstetric bleeding, hypertension, infection, tachycardia, preterm labour, exacerbation of pre-existing condition and pre-eclampsia.
3) Clinician assessment of all SAEs found none likely to be vaccine related.

How reassuring.

Safety of Tetanus, Diphtheria, and Pertussis Vaccination During Pregnancy: A Systematic Review.
https://www.ncbi.nlm.nih.gov/pubmed/28178054

“Of three retrospective studies assessing chorioamnionitis after vaccination, one showed a small but statistically significant increase.”

“Evidence suggests that antenatal combined Tdap administered during the second or third trimester of pregnancy is not associated with clinically significant harms for the fetus or neonate. Medically attended events in pregnant women are similar between vaccinated and unvaccinated groups.”

Begs the question…what would qualify as a “clinically insignificant harm” for the fetus or neonate? Also, why use the term “medically attended events”?

SMH

Read a little more closely. The first study is a Phase 1-2 clinical trial. The N=48 is fine for a study that size, and the authors call for further research. The control group was not unvaccinated women. The control group was non-pregnant women. Women who had been vaccinated with any tetanus containing vaccine within the previous two years were excluded regardless of pregnancy status. The non-pregnant women were also followed. These are not flaws in the design.

The second study is an observational study. Again, the authors note the study size as a limiting factor, so what’s the beef? Size in this case doesn’t make the results invalid. Influenza vaccination is a confounding factor; it was acknowledged so it could be controlled for. So what? As for the serious adverse effects, you should have looked past the table in the article. Only 3.9% of participants had a SAE, and time of onset of symptoms varied, making it hard to tie to the vaccine. In fact, the researchers couldn’t tie them to the vaccine.

Finally, your third study: did you even read the study? It doesn’t look like it based on your post, and you only linked to the PubMed abstract. However, I was easily able to obtain and read the actual article. Really, you’re complaining about terminology with medically attended events? THAT is your criticism?

The original studies could not connect vaccination with chorioamnionitis. It’s barely a correlation, much less a causation, and other studies didn’t find a similar risk.

Quit JAQing off.

Yes, the first study is indeed a Phase1-2 clinical trial. Did you notice how this study was presented by Chris Preston (Aug 23 1:58pm)?

“Tdap has already been shown <>. It is not necessary to conduct the same studies on every single brand of vaccine when there is no reason to suspect there will be a different outcome (i.e. the other brands have been shown to be safe in other population groups).”

I need to correct myself, for the pregnant women in this study they were assigned 2:1 to receive vaccine or saline placebo, the age-matched comparison group of non-pregnant women was in addition to that. So they did have a control group. But I’m not sure what adverse reactions they were hoping to capture with N’s of 26 and 12 respectively.

For the second study, a rate of serious adverse events (SAE) of 1 in 26 is very high, and cause for alarm. But not to worry, they were not caused by the vaccine. How convenient, you do a safety study to look for patterns in adverse reactions, then when you find them, you simply declare them unrelated to the vaccine.

@David,

Shifting the goal posts again, I see.

The N number in a Phase I clinical trial is always small because you don’t want to create tons of side effects in a population. Phase 1 trials are about safety not efficacy, and especially with pregnant women a large group could create ethical problems. It doesn’t make the results invalid. Explain why you think it’s too small, and back it up, and we’ll have something to talk about. Don’t change the subject to Chris Preston and never address it.

As for the second study: the rate of SAE’s in TDaP vaccination was NOT 1 in 26. You’re quoting out of context AGAIN. All you did was divide the number of participants by the SAE’s. The rate of SAE’s associated with vaccination is actually zero, because when the researchers looked at cause NONE of the SAEs can be linked to vaccination.

This happens for various reasons: the wide variability between the event and the administration of the vaccine is one. Others, like trisomy 11, are genetic issues that have nothing to do with the vaccine.

If the SAE’s had actually been linked to the vaccine, then 1 in 26 would indeed be alarmed. That none of those were linked to the vaccine itself means there’s no reason to worry.

It’s up to you to prove that those SAE’s were linked to the vaccine and not something else.

This is the “science” y’all believe we

TINW. Now, please defend that apostrophe. Protip: It’s not a contraction. But you’re an all-around expert.

” But I do have a BS in mathematics with emphasis on probability and statistical methods and a BS in psychology with emphasis on experimental design, so I do know how to interpret a study and I know my statistics. Fair enough?”

No. this means you should have some understanding. Even with that, having the training and being able to see past one’s biases (case in point: Brian Hooker) are also separate issues.

It is all motivated reasoning. Hooker, Foster and others (like that statistician from Kansas) are reading the numbers through their biased lenses. It is just one reason why they refuse to look at relative risk.

Why don’t you tell me precisely what it is I am not understanding? Instead you simply insult and insinuate.

That this study is flawed is really quite simple to understand. The timing of the data collection period and the cutoff end date are inappropriate, especially when the numbers for vaccinated vs. unvaccinated pregnant women are not evenly distributed throughout the cohorts. And the different is not subtle, we’re talking something like 25% in 2011 vs. 75% in 2014 (I am being lazy and estimating here…but this is close). This means that most of the vaccinated women are from the later years of the study, and the authors indeed found that the vaccinated women had a significantly shorter followup period, by 6 months. And interestingly enough, this 6 months falls on the low side of the average age of autism diagnosis, so this would definitely mean that cases of autism could easily be missed.

As if this isn’t bad enough, they allow mother/infant pairs into the study when the baby was enrolled for 90+ days but then un-enrolled, instead of excluding them from the study which is what they should have done. This adds even more bias as some of these children could later be given an autism diagnosis, within the followup period, but be counted in the study as non-autistic.

But all it takes for all of you vaccine apologists to look past all of this is simply for the authors to throw out the word “stratified”…that’s the ticket. That fixes everything. What a crock! With the uneven distribution of vaccinated vs. unvaccinated women and significantly shorter followup periods for the vaccinated women, all this does is create multiple smaller biased studies with less power and little probative value.

Again, no.
A. Vaccinated v. unvaccinated: While you’re right that there are a lot more vaccinated women in the last cohort, the total is still more unvaccinated. The rates of autism between the 2014 group are not that different from those in the other years, and even if we said some vaccinated cases of autism were missed – something you’re assuming, and assuming they’re many of them – let’s say they bring the rate in the vaccinated group to 1.5 or even 1.6: still wouldn’t change the final result. The authors addressed the birth year issue by pointing out that “because we identified minimal variability in study results when stratifying by birth year, these variations likely did not affect our results.”

It’s not throwing around the word “stratified” – it’s explaining that the authors examined the results in several ways to account for differences.
Your assumption that this makes a difference has no basis.

t

I think it takes a lot of wishful thinking to see this as a serious flaw. Groups were pretty similar.

B. Termination of membership:
I. You’re writing it wrong again. It’s 90 days past the age of 1. Not 90 days. The rates of the total kids excluded were: “Approximately 15% of children in the unvaccinated and 13% in the vaccinated group did not have complete follow-up through the end of the study because of termination of KPSC membership.” So close across both groups. You are assuming many of them left soon after the 90 days, and then that this would somehow skew the results – but you give no basis for assuming that. There are more vaccinated kids than unvaccinated diagnosed at the earlier ages – it’s still not clear why you think this exclusion, very close across groups, is an issue.

I understand that the results of the studies go against your deeply held believes. But it’s a large, careful study. Retrospective studies like this are going to have some differences in the study population; It’s the nature of the beast. Without strong reason to think these differences would affect the results, it doesn’t remove the study. You haven’t given such strong reasons.

all it takes for all of you vaccine apologists to look past all of this is simply for the authors to throw out the word “stratified”

I was more thinking “yobbo.”

It’s cute, but given that I can’t recall the original paper that led me to this position, I will note this item from American Speech, which mainly deals with usage in the singular but otherwise demonstrates the point.

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