That is a good question and I don't know the answer. Everyone I have talked to does not really know what causes it. Some think that the lack of red blood cells in the baby, from an infection or an immune reaction is the cause. There is no evidence that it is hereditary, and several dog breeds are more prone to have them than others and EB are one of them. Also water puppies are impossible to deliver naturally, because they are too big for the birth canal and a C-section is a must. Hope this helps. I'm sure there will be someone here that may know the complete answer.