Is a vanity address sufficiently secure if I generate it and the paper wallet offline and assume my computer has no malware?
If it is properly generated? Yes.
And the impossible question... is bitcoin a reasonable risk for such a long term investment?
It's much better than a lottery ticket. If bitcoin reaches mainstream use in her lifetime, she'll be absolutely amazed at your foresight and extremely thankful for your generosity. If bitcoin fails and disappears into a footnote in financial textbooks, then she'll be mildly entertained at your naivete and gullibility. Either way its a fun gift that will come up in conversations years later.
So I guess my real question here is has anybody else done this or put bitcoin in cold storage for a similarly long period?
I've helped both my sister and my father put some bitcoins into cold storage back in 2013. Both of them plan to just ignore the daily fluctuations. If there is suddenly enough value to retire early, they'll cash out (or simply start spending bitcoin if it has REALLY gone mainstream. If it never reaches that value (or collapses completely), the money is already out of mind and considered "spent", so nobody will be devastated at the loss.
And are there any other considerations I haven't thought of?
Your biggest concern will probably be that the piece of paper could either get lost, damaged, or the ink could fade and become unusable.
The next concern would be someone getting a hold of the paper wallet that decides to take the bitcoins without permission (family member, future boyfriend, etc).
Assuming that the paper wallet is created in a secure manner, and that it lasts 15+ years, and that the bitcoins haven't been stolen before your niece can access them...
You might want to think about whether you (or anyone else in the family) will want to contribute additional bitcoins in the future. My suggestion would be to generate new paper wallets for each gift in the future and not to re-use the existing address. That will make it easier to cash in just some of the gifts without risking the others, and if any of the paper wallets are ever created on a compromised computer, it will only effect that one gift and not all the others.
One other thing to keep aware of is how technology advances over the next decade or two. Occasionally technology can make sudden leaps and if a mathematical weakness is discovered in ECDSA or any of the hashing algorithms that bitcoin uses, then bitcoin could transition to a new address format. If that happens, old addresses would almost certainly still be valid, but they might not be as secure. You'd want to generate a new address using the new address system and send the bitcoins from the paper wallets to the new address system to keep them safe.