Folic acid and autism

Aurelian Muntean writes:

I have read an article on NPR and the journal article that spun this news.

What draw my attention was the discussion in terms of causation implied by one of the authors of the article interviewed in the NPR news, and also by the conclusions of the article itself claiming large effects.

Although the total sample (self-selecting pregnant women) seems very large (85,176) the subsamples (270 out of which 114 were in the sub-subsample revealing statistically significant association) used to support the analysis seem to be too small. Or not?

My response:

The different sources of information do seem to be in some conflict:

- The JAMA article reports the autism rate of 1 per 1000 for children of mothers taking folic acid and 2 per 1000 for children of mothers not taking folic acid. (They also report the adjusted odds ratio as 0.6 rather than 0.5, indicted that the two groups differ a bit in some background variables.)

- The NPR article has this quote: “‘That’s a huge effect,’ says Ian Lipkin, one of the study’s authors . . . ‘when you start talking about autism, a disorder that has an incidence of 1 percent or higher, that really does bring it to home,’ Lipkin says. ‘That is a substantial risk.’” How do you get from 1 or 2 per 1000 to “1 percent or higher”?

Another issue that arises is multiple comparisons: they studied at least three subpopulations (“114 with autistic disorder, 56 with Asperger syndrome, and 100 with PDD-NOS”) and at least two predictors (“Similar analyses for prenatal fish oil supplements showed no such association with autistic disorder”). So it seems like we’re seeing the most statistically significant of at least 6 comparisons.

In general I recommend addressing multiple comparisons problems by using hierarchical models, but it’s not clear to me exactly what I would do in this case. It would be good to have a general method to recommend for this sort of problem. I think it would involve regularization and informative priors.

Finally, there’s causality—do the folate and non-folate parents differ, on average, in important ways not controlled for in the analysis? I have no idea. I will say, though, that we followed the folate recommendation ourselves.

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