I have long considered Paul Offit MD as one of heroes and leaders of the public discussion of how vaccines save lives, and how they have made the lives of the world’s children healthier and better. Dr. Offit, together with Edward Jenner (the father of immunology), Jonas Salk (discoverer of the polio vaccine), and Maurice Hillman (inventor of the MMR vaccine against measles, mumps and rubella), should have statues place outside of every pediatric hospital in the country for the number of lives that they have saved.
The vaccine deniers constantly repeat untruths about Dr. Offit so that those lies eventually evolve into apparent truths, at least for those who hold onto their pseudoscientific anti-vaccine beliefs.
The problem is, of course, that if you’re a new parent who is confused by what vaccines may or may not do, you’d assume you could not accept anything that Dr. Offit says because of those Big Lies, and many of the ridiculous tropes and memes of the vaccine denialists. And this is sad.
This post examines the treatment by the National Vaccine Injury Compensation Program (NVICP) of the first of two claims (see second one here) heard from those claiming vaccines cause more injuries than acknowledged in recent days. This article will focus on vaccine injury compensation and mitochondrial disorders – while the second one will cover an NVICP decision with respect to a form of an autoimmune syndrome.
The Special Master’s decisions – as many decisions in NVICP are – are long, complex, and examine the evidence closely and in detail. They address factual debates, expert disagreements specific to the case and expert disagreements on the science.
This post won’t cover them – that’s not my goal. All I will address are the Special Master’s conclusion about two hypotheses raised by those who believe vaccines injured their child (and also promoted by anti-vaccine organizations).
The NVICP (commonly called the Vaccine Court) is a no-fault program created by Congress to serve two goals: to protect the vaccine supply by offering limited liability protections to vaccine manufacturers and providers and to help those injured by vaccines – or even those who may have been so injured – be compensated more easily than in the regular courts.
NVICP is not, however, a benefits program. Its goal is not providing any parent with a child with a problem support. The United States certainly needs to offer more support to families of children with disabilities, but NVICP’s aim is different: it focuses on compensating injuries that may, at least, have been caused by vaccines.
To be compensated by an NVICP decision a petitioner does need to meet minimal standards suggesting a possible connection between a vaccine and an injury (a settlement does not require similar proof; parties settle for all kinds of reasons, including a view that the case isn’t worth litigating). At the very least a petitioner needs to show an injury, and provide expert testimony (expert testimony is generally needed when someone claims medical causation in the courts as well – that a medical act, device, drug etc. caused harm – with very narrow exceptions).
The documentary claims that there is a conspiracy by the CDC to hide the link between MMR and autism, even though the documents supposed to support that conspiracy do not support such accusations. In spite of the fact that even if the CDC wanted to hide such a link, it couldn’t control studies done in other countries looking at the issue (and finding no link). It makes untrue statements about vaccine testing, like falsely claiming that vaccines are not tested in combination.
In addition, in several cities, the Vaxxed team – discredited scientist Andrew Wakefield, his collaborator Polly Tommey, and producer Del Bigtree, and occasionally others – followed certain screenings with a question and answer session. In those sessions they made false claims that could mislead parents away from protecting their children by vaccinating.
The Vaxxed team claimed that preventable diseases were not prevented by vaccines. Among other things they claimed that vaccines were both ineffective and unsafe, ignoring abundant research showing the opposite: modern vaccines are extremely safe and effective.
Del Bigtree falsely described the hepatitis B vaccine – that protects against a virus that can cause liver disease and cancer – as “injecting a sexually transmitted disease”, potentially scaring parents off protecting their children against this dangerous infection. Finally, the Vaxxed team warned listeners against seeing pediatricians, because they can’t be trusted (see here and here for more of their misrepresentations and misinformation).
If a viewer watches Vaxxed and listens to the team’s advice, decides not to vaccinate based on this misleading information, and their child gets a preventable disease and is harmed by it, can they sue for money damages in torts?
This last week or so, every day seemed to bring a new finding about something linked to autism. I blogged one of them — diabetes — but who really would have the wherewithal to follow the growing list of factors linked to autism? I guess I would because below, I give you that very list, including current pop hits and some blasts from the past, with some brief commentary. Without further ado — The ever-changing face of autism — or, as some have wisely suggested we call it — the autisms.
What causes autism is a question that does not have “vaccines” as the answer. And despite all of the memes, Facebook groups, and nonsense pushed by pseudoscience websites, like Age of Autism, science actually has a pretty good idea about what causes autism. And let me repeat it once more, it isn’t vaccines.
What is autism spectrum disorder
I’m not going to go into all the details about ASD diagnosis, symptoms and treatments – that would take up a book. But, I will spend a bit of time defining what constitutes autism spectrum disorder. ASD is a range of different conditions classified as neurodevelopmental disorders in DSM-5. However, individuals diagnosed with ASD must present with two general symptoms:
Deficits in social interaction and communication
Repetitive and restricted patterns of behavior interests or activities
Furthermore, there is a range of symptoms from minor to severe, with each person with ASD expressing it in an almost infinite variety of symptoms and severity. Although ASD is considered “incurable,” it is not a sentence of a mental prison for the patient. The lay public tends to box ASD children into one small stereotype, like people do with most mental health disorders, despite the fact that there is huge variability in how a child expresses ASD.
Although evidence-based interventions for autistic children vary in their methods, many adopt a psychoeducational approach to enhancing cognitive, communication, and social skills while minimizing problem behaviors. It has been argued that no single treatment is best and treatment is typically tailored to the child’s needs.
I think the most important thing to note about ASD is that it is a complex disorder with a wide range of symptoms. It’s not a “death sentence” for either the parents or child, despite what you may have heard on the internet.
What causes autism – genetics
The best evidence we have is that ASD is a genetic disorder. Researchers first recognized genetics as the foundation of ASD in the 1970s. Studies on twins showed that monozygotic twins (genetically identical) were more likely to share a diagnosis of ASD than dizygotic (non-identical) twins. That is a strong indicator of a genetic relationship to ASD.
More recently, a large population study, which included over 7,000 pairs of twins, provided further evidence of a genetic link for ASD. The authors concluded that,
Genetic factors underpinning individual differences in autism like traits show considerable overlap with genetic influences on diagnosed ASD.
The big question that remains is how do these genes affect the brain that leads to ASD. Research is moving to examining those gene mutations that increases (or decreases) the risk of developing ASD.
I know that there is a tendency to want to blame something for ASD. It’s a hard realization that ASD is related to one’s genes that they pass on to their children. But there’s no blame there – it’s how genes randomly combine to form your child.
What causes autism – exposure to infections and medications during pregnancy
Let’s be clear – not everyone with the genes discussed above has ASD. Because mutations to genes alone may not be solely responsible for ASD. Once a child has an underlying genetic predisposition or mutation to ASD, it may take a trigger from an environmental factor to fully cause ASD.
This is where the science starts to get a little hazy – there are tons of different potential environmental factors that might contribute to or trigger autism. And no, vaccines are not one of them, that’s been dismissed by scientific evidence. But other contributors are still in the hypothesis stage – pollution, pesticides, anti-depressants, and viral infections. Unfortunately, like Dr. Willingham implied, there are a bunch of hypotheses that lack robust evidence to support them. In many cases, we have robust evidence that the hypothesis is completely wrong (did I mention vaccines?).
We have a lot of confidence that there is a genetic pre-disposition to autism. Very robust, repeated, and published evidence. On the environmental side, there is little clarity (except that vaccines are not related – am I repeating myself?).
So what do we have? There is very strong evidence that a rubella infection during pregnancy leads to a significantly increased risk of autism in her baby. Immunization against rubella before or during may be an effective strategy to reduce the risk of autism in children of those mothers.
Despite what you’ve read on the internet, most of the other evidence is weak, conflicting, or downright inconclusive. For example, what about SSRI antidepressants? Actually, a meta-review of anti-depressant use during pregnancy showed no effect on the risk of ASD in babies as a result of antidepressant use by the mother. However, it is possible that depression (not the use of antidepressants) in the mother prior to conception may be an environmental risk factor.
A massive meta-review of environmental risk factors showed either a small correlation to ASD. Or none at all. Here are some of the factors where there is no robust evidence that there is either a positive or negative association between it and ASD:
Preconception chemical exposure
Pesticide exposure during pregnancy
Pesticide exposure during childhood
Heavy metals (including mercury, lead, cadmium, aluminum, arsenic, nickel, uranium, and tin)
Camel milk (yes, camel milk)
Gluten free diet
In fact, the review found only one environmental risk factor that has a strong association with ASD – valproate, a medication used to treat epilepsy and bipolar disorder.
Another environmental factor seems to be strongly linked to ASD – being male. According to research, autism spectrum disorder affects boys about 4X more than girls. It also appears that it takes fewer genetic mutations for boys to get autism than girls. The reason for this male risk factor is unknown, though there’s a lot of wild speculation, including that there might not be sex-based differences in risk, it’s just harder to diagnose in girls.
What causes autism? Still not vaccines
After reviewing the evidence, we know two things for sure:
Vaccines are not related to autism.
Genetics are related to autism.
Other than those two scientifically supported conclusions, research is still ongoing and is mostly inconclusive. So why do some parents still want to blame vaccines? There are probably a lot of reasons, but mostly it’s because they ignore the ironclad conclusive evidence about vaccines and ASD, and focus on the general lack of strong evidence in other areas.
The evidence about autism and genetics is complicated and not prone to a simplistic, one-sentence descriptions. It’s easy to wrap your arms around it like “vaccines cause autism” – it’s simple and easy to state. On the other hand, there’s the little issue that if your child has autism and that’s a result of genes, those genes come from only two places – the mother and father. Maybe its just easier to blame vaccines or gluten in the diet rather than accept that one’s own genes are to blame.
There is a boatload more research that needs to be done for us to completely understand what causes autism spectrum disorders. But we have a boatload of evidence that it’s not vaccines.
One of the enduring zombie myths pushed by the anti-vaccine side is that their children are healthier than vaccinated children. But are vaccinated children sicker? Not based on any real, scientific evidence. But that never stops the science denying anti-vaccine crowd.
In any case, I take some comfort in the hilarious result of this survey that demonstrates that autism prevalence in the unvaccinated is similar to autism prevalence among the vaccinated, no matter how much anti-vaccine activists try to spin it otherwise. I realize that this survey is in fact so poorly designed that it really doesn’t tell us much of anything, but it is fun watching anti-vaxer brains explode trying to spin this result as supporting the vaccine/autism hypothesis.
Now we have a new study that barely rises to the same abhorrent quality level of the aforementioned German study. Of course, we have to look at it.
Vaccinated children sicker – the research behind the myth
The claims that are circulating across the anti-vaccine blogosphere are based on a recent article published in the Journal of Translational Science. Before we get into the article, you might be wondering what is “translational science,” because it sounds a bit woo-based. Translational medicine or science is an interdisciplinary approach which combines resources, expertise, and techniques within basic sciences to discover enhancements in prevention, diagnosis and therapies for various diseases. It’s actually pulling medicine back to basic sciences to better understand everything going on in the body.
For example, they may discover a mutated gene that produces a dysfunctional protein that has a profound effect on the body. They then target that gene and its protein production to treat the disease, rather than target the symptoms that are caused by the bad protein. Translational medicine is an exciting field of biomedical research, on which has shown much promise. However, some “translational medicine” has moved into the world of woo.
Here’s what the Journal of Translational Science (JTS) says its goals are:
JTS is a novel journal that will focus upon the translation of cellular, molecular, and genetic pathways into clinical strategies for multiple medical disciplines that can impact a broad spectrum of disorders that involve stem cells, degenerative diseases, aging, immune function, tumorigenesis, epigenetics, musculoskeletal function, cognition, behavior, neuronal, cardiac, pulmonary, gastrointestinal, and vascular targets, and metabolic function overseeing all aspects of translational research and medicine. JTS will provide a platform in today’s scientific and medical literature to serve as an international forum for the healthcare and scientific communities worldwide to translate novel “bench to bedside” science into clinical therapies as well as report upon prognostics, novel therapeutic strategies, and biomarker development.
That’s all well and good, but the study from JTS that we’re discussing in this post doesn’t fit in any of those. And a review of much of the research they publish is laughably woo-based. In the same issue of JTS as the article we’re discussing, they had published an article examining traditional Chinese medicine, which is neither traditional nor medicine.
So, let’s take a closer look at the “vaccinated children sicker” paper.
A 10,000 meter meta critique of the paper.
There’s a lot to dislike about this paper and journal. But I think it’s important to take a meta-approach to this paper to make sure you have a good grasp of the quality of what we’re critiquing.
The Journal of Translational Science is not indexed in PubMed. It’s been over two years since the journal was first published, and it is rare for a journal to not be indexed there. Without PubMed, it is extraordinarily difficult to cites one of the articles published in JTS. Of course, there’s no reason given for it’s exclusion from PubMed, but we can speculate that possibly the science is bad.
JTS lacks an impact factor. The impact factor gives us a relative understanding of the quality of a journal – generally, the impact factor tells us approximately how many times an average article published in a journal is cited per year. A journal like Nature has an impact factor of 36, which means the average article is cited 36 times a year. Why is this important? We know that more pivotal and valuable research is cited many times and often repeated by other scientists, especially in new publications. This is how science develops solid evidence, by examining and repeating the findings of others.
The publisher of JTS, OAT, is a predatory publisher according to the definitive Beall’s List of predatory publishers. A predatory publisher is “exploitative open-access publishing business model that involves charging publication fees to authors without providing the editorial and publishing services associated with legitimate journals.”
Low impact factor, predatory journals are generally dismissed by scientific researchers because the peer-review is weak. These journals are often abused by researchers whose data has been rejected by one or more of the respected journals, so they settle for these low quality versions. In the academic community, publications such as these often cannot be used as evidence of qualification for tenure.
None of these issues alone should lead one to dismiss the data outright. However, if one had real data that leads to a conclusion that “vaccinated kids sicker – watch out,” it would have been accepted by any of the journals that have focus on vaccines. But if the research was not well-designed, and well-analyzed, then the better journals would move away, and quickly, from adding it to their publication.
Critique of the “vaccinated children sicker” paper
The authors, Anthony R Mawson et al., hypothesized that there was an association between vaccines and neurodevelopmental disorders (NDD) of 6- to 12-year old biological children. The study was of home schooled children in Florida, Louisiana, Mississippi and Oregon. The mothers were asked to complete an anonymous online questionnaire on their children with respect to pregnancy-related factors, birth history, vaccinations, physician-diagnosed illnesses, medications used, and health services utilized. The NDD was defined as having one or more of these diagnoses – learning disability, attention deficient hyperactivity disorder (ADHD), and autism spectrum disorder (ASD).
The study found the following conditions were more prevalent in vaccination children:
Allergic rhinitis (odds ratio = 30.1). We’re going to take a look at odds ratio down below.
Other allergies (OR= 3.9)
Eczema/atopic dermatitis (OR=2.9)
Learning disability (OR=5.2)
Any chronic illness (OR=2.4)
Well, all that sounds like vaccines are worse for our children. Except it really doesn’t.
How about we jump in with a harsh critique of these kinds of studies:
It uses an internet questionnaire to determine each of the data points for this study. The use of questionnaires for epidemiological studies is frowned upon by many researchers. The reasons for this are many, but they include a reliance upon the memory of the participant for events that may be not be recalled correctly. In addition, there might be intentional or unintentional bias of the survey participants towards relating a condition to vaccines or ignoring one in unvaccinated kids. Better done, and frankly, more expensive, epidemiological studies rely upon medical records to reduce errors in memory and bias. This is a critical point – the best studies that show no link between vaccines and autism rely upon actual medical data for each child, not on a questionnaire which may or may not be tracking accurate information.
Home schooled groups are unrepresentative of the school age children at large. Many children are homeschooled because of parents dislike of vaccinations, so this forms a biased group. Now, maybe the home schooled group mirrors a traditionally schooled group – if you want to make that case, then you need actual data published in an actual journal.
Parents who do vaccinate may be less reluctant to visit their physician to get diagnosed for diseases, while a non vaccinating parent may choose to ignore any health issues as minor. Thus, there may be an unintentional bias towards health care issues for vaccinated children.
The groups (vaccinated vs. unvaccinated) are not randomized which will lead to observational and confirmation bias.
There was a lack of analysis of potential cofounders which might bias the results. Were there other differences between he vaccinated and non-vaccinated groups that could have biased the results one way or another?
The use of odds ratio by the researchers is curious and may have biased the results. The only reason to use OR is to inflate the difference between both groups. Real epidemiologists prefer relative risk (RR) which provides us with a much more sensitive understanding of the incidence of a condition in a vaccinated group vs. an unvaccinated group. For example, the RR for ASD from this study (if the data actually were useful, which it isn’t) is 3.1, whereas the OR is 4.2.
The over reliance on p-values is always a red flag to researchers. With so many p-values, the probability of false positives is fairly large. Because the population for the study was so small, it’s also worth nothing that the OR had relatively large error brackets, most of which crossed near unity, that is, 1.0, indicating no difference between the groups.
The authors seem to overlook or ignore the point that the vaccinated children had much lower risk of diseases like chickenpox and measles, which we know bring with them significant risks of long-term health issues. Even if we accept this poorly designed study as providing us with evidence of harm from vaccines, one would have to balance it against the benefits of avoiding vaccine preventable diseases. Of course, this study is so bad, it’s hard to accept anything useful from it.
Predictably, the authors conclude that:
First, additional research is needed to replicate the findings in studies with larger samples and stronger research designs. Second, subject to replication, potentially detrimental factors associated with the vaccination schedule should be identified and addressed and underlying mechanisms better understood.
This pilot study shows us that if mainstream medicine and our public health agencies are really interested in children’s health, not just vaccine profits or defending vaccine religion against blasphemy, what is needed is not the will to make everyone believe, but the courage to find out.
But real science says that the study used by this anti-vaccination believer is poorly designed, and it does not show what they claim it shows. It’s biased, poorly analyzed, and comes to conclusions that are not supported by the vast mountains of real science published in real (read, non predatory journals). No real scientist would accept the findings of this paper, other than to laugh heartily. I don’t laugh, because I know some crackpot will use it to “prove” that vaccines are dangerous, when there’s no robust evidence to support that belief.
Recently, an anti-vaccine doctor from Oklahoma, Dr. Jim Meehan, wrote an online post about why he would no longer vaccinate his children. It’s pretty clear that his post is not so much a discussion of his own children (most of whom are adults) as an attempt to deter other parents from protecting their children from preventable diseases. His post is basically a set of claims trying to convince parents that vaccinating is very dangerous.
The claims used to do so are nothing new: they are strictly out of the anti-vaccine playbook. But the post has received some attention in the anti-vaccine world, and was shared several thousand times, likely because many people treat an MD as an authority on the subject. So I decided to take a few minutes to explain why his claims are not good reasons to reject expert opinion and not protect children from disease.
Dr. Meehan’s claims fall into several categories (which will be discussed individually below):
The diseases we vaccinate against are not dangerous, and it’s okay, even good, to encounter them naturally.
Vaccines have toxic ingredients.
Vaccines are dangerous to children.
The science behind vaccines is corrupt because the pharmaceutical industry controls it and corrupts it.
We should listen to him because he is a doctor and knows what he is talking about.
I have written more about the question, “are vaccines and autism linked?,” than just about any other topic other than the cancer preventing HPV vaccine, Gardasil. Unless you want to ignore the overwhelming evidence, the scientific consensus is pretty clear – vaccines are not linked to autism.
In my article, Vaccines and autism – science says they are unrelated, I list out over 125 published, peer-reviewed articles (as of today) that basically provide us with some of the overwhelming evidence that debunks the myth that vaccines cause autism. But that’s a long list that takes quite a bit of time to absorb. I think it’s more important to focus on the handful of the best studies that provide the best evidence. I hope this kind of resource helps you refute arguments from patients, friends, and family members who might try to claim that “we don’t vaccinate because of the autism risk.” I can’t guarantee that a few important studies will convince anyone, but maybe it will help with a fence sitter.
I’m relying upon Dr. Peter Hotez’s article, The “Why Vaccines Don’t Cause Autism” Papers, published in PLOS Blogs to choose the best of the best papers. I’m going to add a couple of more categories, because they discredit some of the arguments that try to state that the answer to the question, are vaccines and autism linked, is yes.
Vaccines and autism are not linked or related according to real science, published in real scientific journals written by top scientists and physicians.
But this false claim is in the news again. Probably as a result of reports that more and more children are being diagnosed with autism spectrum disorders. So let’s take a look at the science.
On 28 March 2014, the United States Centers for Disease Control and Prevention (CDC) announced that new data show that the estimated number of children identified with autism spectrum disorder (ASD), a disorder of neural development, usually appearing before the age of 3 years, characterized by impaired social interaction and verbal and non-verbal communication, and by restricted, repetitive or stereotyped behavior, continues to rise. The picture of ASD in US communities is changing. Continue reading “Vaccines and autism – science says they are unrelated”
Recently, Dr. Rachael Ross, who gained fame when she was on the medical talk show, The Doctors, has written a letter that suggests she now subscribes to a large number of anti-vaccine tropes. While there really isn’t anything new in the letter – the claims in it are far from original, and have been repeatedly shown untrue – as a doctor, her words carry weight. So Rachael Ross gets Vaxxed – it’s worth responding to her.
I don’t know what drove Dr. Ross to promote anti-vaccine misinformation. It may have been misplaced trust, believing in Del Bigtree, Vaxxed producer, who has been promoting quite a bit of misinformation recently, some of it incredibly harmful. She may have already been susceptible. Maybe all of the above. It doesn’t matter.
She chose to speak up, and whatever her intent, the result is that she provided ammunition to anti-vaccine activists and anti-vaccine parents that can be used to sway others away from protecting children from disease. Dr. Ross includes in her letter the mantra of “do no harm.” But a letter promoting this kind of misinformation – by a doctor, with the authority the profession confers – is very likely to do harm. It’s unfair to the children denied vaccines because of it. Continue reading “Rachael Ross gets Vaxxed – that’s never good for a real doctor”
I have been unwavering on this one point – there is no link between the MMR vaccine and autism spectrum disorder (ASD). They are simply unrelated, based on high quality evidence published in respected peer-reviewed journals across the world. To dispute this conclusion, using only low quality evidence published in predatory and low impact factor journals, is the epitome of science denialism.
There are some interesting early results from a study, published in Nature, that is examining brain development in infants who are at risk for autism spectrum disorder. The study hasn’t uncovered any new information about what may cause autism, but it did confirm that the MMR vaccine is unrelated to autism. Throw this study onto the mountain of evidence that completely debunks that myth.
The ongoing study’s results indicates that changes in the brain in early infancy may be predictive of an autism diagnosis at age 2 in children who have higher odds of autism because an older sibling has been diagnosed with ASD. The researchers took MRI images of the brains of children at higher risk at ages 6, 12, and 24 months, along with administering a test at age 24 months that assists in the diagnosis of autism along with another test that evaluates social skills.
The early results (the final paper will come out within a year or two) suggests that rapid growth of the surface of the cerebrum from ages 6-12 months preceded an increase in brain volume at age 12-24 months in children at risk for ASD and who were diagnosed with ASD at 24 months. Based on this cortical surface growth, the researchers were able to predict an ASD diagnosis in 81% of high risk children who eventually were diagnosed with ASD.
Again, this study didn’t provide us with any information about possible causality for ASD – it provides us some evidence of predictive diagnostic methods. Moreover, the study had a relatively low study population, and we really need repeated studies to confirm the value of this study.
Emily Willingham, writing in Forbes, does a rather thorough review of the study for those interested in the predictive ability of the study. She says this about what this study says about any relationship between the MMR vaccine and an ASD diagnosis:
Finally, these changes before age 12 months that are associated with a later autism diagnosis precede the timing of administration of the MMR vaccine. This vaccine, readers may recall, is the one that true-believer anti-vaccine activists consistently promote as causative in autism. According to the vaccination schedule, it is administered at age 12 months. These latest detected changes arise before that age, but the rapid growth associated with them kicks in right at about age 12 months, once again illustrating that coincidence of events doesn’t always mean their association.
Dr. Willingham states that the changes that precede a diagnosis of autism appear well before the first administration of the vaccine. The first MMR vaccination just happens to be coincidental to the rapid growth that is associated with ASD. Remember correlation doesn’t imply causation, especially now that we have evidence that the brain changes indicated in ASD occur prior to administration of the MMR vaccine.
I know that the “true-believer anti-vaccine activists” will be unconvinced by this evidence, and that is sad. There is simply no evidence that MMR vaccine and autism are related. In fact, evidence suggest that they are not related.
The MMR vaccine saves lives, so let’s just protect our children with it.
Hazlett HC, Gu H, Munsell BC, Kim SH, Styner M, Wolff JJ, Elison JT, Swanson MR, Zhu H, Botteron KN, Collins DL, Constantino JN, Dager SR, Estes AM, Evans AC, Fonov VS, Gerig G, Kostopoulos P, McKinstry RC, Pandey J, Paterson S, Pruett JR, Schultz RT, Shaw DW, Zwaigenbaum L, Piven J; IBIS Network.; Clinical Sites.; Data Coordinating Center.; Image Processing Core.; Statistical Analysis.. Early brain development in infants at high risk for autism spectrum disorder. Nature. 2017 Feb 15;542(7641):348-351. doi: 10.1038/nature21369. PubMed PMID: 28202961.