So you mean it's likely these expecting mothers were undermethylators? (If undermethylator given my scant knowledge of this stuff means is "slow to convert folate into methylfolate" so the unconverted folate remains in the blood?)
I wouldn't use the term undermethylation. This concept, along with the converse overmethylation, has wide claims made for it with not much evidence. Since many of the symptoms supposedly attributable to the two conditions overlap, I am skeptical about the notions behind the claims.
High levels of substances in the blood may mean they are being supplied in excess but they may also mean that there is not much call for them in the cell; the metabolic pathways using them are proceeding slowly. Conversely low levels may mean poor supply, but may also mean excessive demand. The pathways using them in the cell are proceeding at a high rate.
So blood levels alone are not sufficient to work out which possibility is actually occurring.
I was pointing out that there is evidence for both B12 and folate that high levels in blood can mean that the vitamins are not being taken up into the cell - ie they are not being transported or the pathways using them are proceeding slowly. The high levels in blood are flagging that there is actually a functional deficit of the vitamins in the cell.
The authors of the paper you linked didn't consider this possibility at all but it is quite possible that the group showing a higher incidence of autism had a functional deficit, not an excess.
In the case of folic acid supplements, this could be contributing to the problem.
Here is one of the papers I couldn't find yesterday. The studies described show that the enzyme DHFR is 1,300 times as slow to process folic acid as it is to process its natural substrate DHF. Furthermore, there is a 5 fold natural variability in DHFR activity among healthy individuals.
So everyone has limited capacity to process folic acid and there is plenty of evidence for widespread accumulation of unmetabolised folic acid in blood among people consuming modest levels of supplements or just from eating fortified foods.
As the paper shows, folic acid inhibits the DHFR enzyme, so the people with the lowest natural levels of enzyme activity may accumulate considerable amounts. This has a cascading effect. High levels in the cell inhibit uptake from the blood so blood levels rise (ie those with the highest blood levels could be those with the slowest ability to process folic acid). Inside the cell, low DHFR activity means that DHF accumulates and this in turn inhibits a number of enzymes in the folate cycle.
So the whole folate cycle slows down, not just the conversion of 5,10 methylene THF to methylfolate (the MTHFR reaction). For people who already have slowed enzymes, such as by the SNPs you are concerned about in this thread, folic acid could exacerbate their problems.
