Harriet Hargrave made a quilt out of unwashed flannel to prove that quilting stops fabric from shrinking. I actually saw that quilt! I'm pretty sure she used Hobbs 80/20 in that quilt, which has a shrinkage rate of about 3%. It was a soft, beautiful quilt that had been washed several times. There was no distortion.
From what I have observed and learned since then, I would say that a lot depends on the batting you use and perhaps even more on how much quilting is done. Basically, as long as you have a lot of machine quilting in the quilt, the batting is going to control how much the quilt shrinks. Quilting will keep fabric from shrinking more than the batting shrinks.
Given what I have seen in terms of flannel shrinking, I would probably hedge my bets by prewashing the flannel once. When you wash flannel, the majority of the shrinkage happens in the dryer.
My thinking is that if you prewash the flannel just once (I usually prewash and dry flannel twice, as it can shrink additionally the second time around) you will have gotten rid of a lot of the excess flannel shrinkage. As long as you use a batting that shrinks a little, and as long as you do sufficient machine quilting, the entire quilt sandwich should come out fine.
I would probably avoid 100% poly batting just because it doesn't shrink at all. Although theoretically the quilting would stop all of the fabrics from shrinking more than the batting, in reality I think you would get a better look by having all three layers shrink a little. I consider 3% to be about right. Hobbs 80/20 isn't the only batting with that shrinkage rate; lots of other battings have it as well. Check the batting specs to find out what the average shrinkage rate is before choosing the batt.