As mentioned here by Ed, some effects are no heart drops from bosses and curses being more prevalent.
I'd hazard to guess that less drops in general and higher HP enemies might play a part. Especially less drops.
And here's his general notes copied over from the linked post:
- Beating different goals in Hard mode will unlock new content not unlockable on Normal.
- Beating said goals in Hard mode will also unlock any unlocks that would be gained by beating Normal mode (so you can start on hard if you’d like)
- There will be achievements for Hard mode.
- Hard mode will have some visual hud/menu changes so you are always aware if you are playing on Hard. (or watching someone play on Hard)
I've asked the same question on the SteamCommunity Forum, and this is the outcome:
Nope, they don't sadly.
I know because I've tried it, was getting
nothing but Breakfast which meant I had exhausted the entire pool. But
none of the items that I needed to find were in the collection page.
EDIT:
There are different opinions, so it's a bit confusing, another guy posted this answer:
I haven't unlocked these yet and somehow they're there.
Meaning that he hasn't unlocked The Lost items (The Soul, The Body and The Mind) but they are shown in his collection page.
So it appears to be true.
Best Answer
According to the Rebirth wiki, which by no means claims absolute correctness but could be a nice indicator:
All of them except for Godhead are for beating Mom's Heart in Hard Mode with various characters.
As for Godhead: