Cashing in on fears of autism

Autism has been the subject of much controversy in recent years.  Rates of diagnosis are rising, and many parents-to-be are understandably worried.  Despite the efforts of many good scientists, we still don't have an explanation for most cases, although we do know that vaccines have nothing to do with it. Many unscientific claims are out there, some of them designed to take advantage of vulnerable parents who are desperate for answers. In this climate, any new claim to have found "the" cause of autism ought to be stated very, very carefully, and backed up by solid evidence.

Just recently, scientists at the UC Davis Mind Institute published a study that described 6 antibodies found in the blood of some mothers of autistic children, and much less often found in mothers of normally developing children.  They suggested that these antibodies somehow got into the brains of developing fetuses, causing autism in the children.  They even gave a name to this form of autism: maternal autoantibody-related, or MAR autism.

If true, this study suggests that a test for these antibodies might predict whether or not a child will have autism.

The study seems plausible, and it was published in a respectable journal called Translational Psychiatry.  Unfortunately, though, the study and the way it has been promoted are plagued with problems.

Perhaps the biggest red flag is that the two lead authors, Daniel Braunschweig and Judy Van de Water already have a patent on the proteins described in their paper, and Van de Water is involved with a company, Pediatric Biosciences (PBI), that is already marketing a test to predict autism based on this study.  Van de Water is the Chief Scientific Advisor for the company, which has licensed her patent for this specific test.  The company website claims

"To date, the test has demonstrated 100% accuracy - meaning if a mother or prospective mother has developed the antibodies, then her child will later be diagnosed with AU [autism] or ASD [autism spectrum disorder]."

Wow. This sounds incredibly accurate. This test is apparently the sole product of PBI, and they trumpeted the new study with a press release claiming that

"PBI is developing a diagnostic test based on these findings that will provide physicians with a reliable set of biomarkers for pre-conception … diagnosis of this Maternal Autoantibody-Related (MAR) form of autism."  

PBI is marketing the test to all "women over 30 who are at least 2 times more likely to give birth to an autistic child" as well as other women.

So, with all this hype, and despite the major conflicts of interest of the lead authors, did the study show what they are claiming?  Is this a test that mothers should take?

In a word, no.

First, the study doesn't even answer the right question.  The study looked at antibodies found in the blood of mothers some years after their pregnancy, not during or before pregnancy. Therefore it doesn't tell us whether a test of a pregnant mother will predict anything at all.  Post hoc analyses like this are notoriously inaccurate: for example, it's easy to find factors that predict every presidential election for the past 50 years, but many of them will perform poorly at predicting future elections.  Similarly, finding 6 proteins that distinguish some mothers of autistic children from mothers of normal children, all measured after the fact, tells us nothing about whether we can predict autism in advance.

Second, their striking claim of 100% accuracy is false.  (Their press release only claimed 99%: "A positive result would mean that they have a 99 percent likelihood of having a child with autism if they proceed with a pregnancy.")  But the study provides no such evidence.  What it did show was that 56 mothers (out of 246) had antigens to one of 12 combinations of 3 antigens that they selected.  [Aside: there are many other combinations of antigens that they did not report, and no indication that they properly adjusted their statistics to account for this.] But the study failed to say whether these 56 mothers also had non-autistic children.  If they did, then even the mothers in their own study had a much lower chance than 99% of having an autistic child.  Given that many families with autistic children also have other, non-autistic children, touting an accuracy number like this, without proof, is outrageous.

The study isn't completely worthless: it points to a possible link between antibodies in the blood of the mother and autism in a child.  If Van de Water were truly interested in the welfare of autistic families, she would be focusing on the obvious next step: test a large, randomly sampled collection of pregnant women for the same antibodies.  Then follow them up, over the next few years, to see if the test can predict the likelihood of having an autistic child.  Meanwhile, no one should be selling a test before studies can show that it has some predictive value.

But Van de Water and her friends at Pediatric Biosciences seem far more interested in making money off the fears of prospective parents.  PBI is planning to charge about $800 for their test, which they'll begin selling next year. Stanford University biostatistician Steven Goodman says that they are "peddling false hope that giving birth to autistic kids can be avoided."

A news article in Science last week raised many serious questions about Van de Water's study and its claims.  Several scientists quoted in that article questioned the premise of the study: that antibodies from the mother somehow get into the brain of the developing fetus. Yale scientist George Anderson said the data are too preliminary and the statistics too weak to support a clinical test (essentially the same argument I'm making here).

And what about that 99% claim?  In their interview with Science, Van de Water and Jan D'Alvise (president of PBI) said it

"was not meant to convey likelihood in the statistical sense, but rather the 99% accuracy with which the study demonstrated specificity of the biomarkers for ASD."  

This is unadulterated poppycock. As of this writing, the company website still claims that the test has "100% accuracy--meaning if a mother or prospective mother has developed the antibodies, then her child will later be diagnosed with AU or ASD [autism]."  That claim couldn't be any more clear - or any more wrong.

With all the controversy over the causes of autism, and with the medical community still struggling to correct the tremendous damage caused by Andrew Wakefield's fraudulent study linking vaccines to autism, the last thing we need is an erroneous claim that someone has found the cause of autism.  And it's far too soon to start offering moms a test that tells them they're going to have an autistic child.