How do e-mail systems know when a particular e-mail (a newsletter, for example) is being sent to thousands...?

...of people and thus (sometimes mistakenly) route it to spam folders? I've got an opt-in signup system for my ministry's monthly newsletter, and a lot of people have told me each month that they didn't get my newsletter--but when I suggested that they check their spam box, there it was. How do e-mail systems know when a newsletter or similar e-mail is being sent to thousands of people, and is there anything I can do to keep my newsletter from being routed to spam folders?