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If you really need to just beat Mom once to unlock mods, then The Bible has a special interaction that instantly kills her when used during the fight. It isn't something you should rely on, though, since it isn't something you can get every run, and only works on two of the story bosses.
You can find it in the Shop, Angel Room, and Library item pools. The item The Rosary from Angel Rooms makes it so it's able to appear in every item pool.
The Bible should always work on Mom or It Lives. I believe the only thing in the game that can even cancel the effect is the trinket Broken Remote, which forcefully teleports you out of the room when using your active item. If you're having any problems with it beyond that, I believe it can only be a conflict with whatever mods you have installed.
I only have music mods (original OST and antibirth OST). But after installing the item description mod, I have seen that I was confusing the Bible with the Book of Revelations. they look the same with a different colored cross.