I don't see anything wrong with a very, very gentle, "What is going on? Is there anything you want to talk to me about?"
Gentle, kind, patient.
I could not walk around on eggshells for very long. Mind you, it may not be the time to have a big, deep discussion, but she might appreciate just knowing that you noticed and are in tune with her and can see something different.
Of course, that would be your opportunity to reassure her as best as you can.