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List of things that prevent all kind of progress:
- Seeds (except a few special ones)
- Challenges (except for their reward obviously).
- Daily Runs.
- Reruns and Victory Laps (except for a few specific unlocks).
- (AB+) Any active mod from the mod menu before Mom is killed once on that save (no matter what they do, other saves are irrelevant).
- (Rep) Enabling the debug console in the config files (even if you don't use it).
- Paranoid antivirus programs (or missing rights) preventing the game from creating/editing its save file.
Emphasis added to both as needed to prove that you didn't understand the question. Checking for the "no achievements" mark in a game you start right now would be helpful. (Fun fact: the achievement disabling is tracked based on whether you currently have the console enabled. You can give yourself whatever items you like and then disable it again before you hit a completion mark boss, and you used to be able to give yourself the achievements directly so this probably isn't changing).
I beat boss rush twice already and still didn't get this. I didn't finish either game to the end, only beat boss rush, but still not item :(
Don't refer to the item list, it shows items you picked during runs, not unlocked content.
After beating boss rush, I used a seed that was supposed to have it, but it wasn't where it was supposed to be....