I must object to any mating exercise with the number of abandoned animals in the United States. We exist due to this abandonment! That being said, the risk would be primarily with a large male breed and small female breed. There could be possible injury during mating. This could be avoided by artificial insemination. Then the puppies could be too large for the mother to deliver. The logistics of mating a small breed male to a large breed female would almost certainly require artificial insemination. I would not expect any risk involved with the birth with the female as the larger breed.