The New Madrid fault has to precede the New Rockies which go back 65 million years or so. The Mississippi couldn’t precede the last ice age which ended 12,000 years more or less, ago. During the last ice age, as well as previous ice ages, the lower Miss. couldn’t have been more than a creek.
The very massive, and frightening series of New Madrid quakes 200 years ago can happen again. If it does, St. Louis will not be a happy place. However, I have read other reports that suggest that the really bad ones happen there more on a 400 year schedule. Don’t remember where I saw that, but have been interested in NM for years. Caracas, Venezuela had a severe quake in that period that killed 20,000.