It is tough to say which are the two main ones.. There are random birth defects as well as those that are caused by something the mother and even father did before birth. In other words, something that happened during the pregnancy. Remember that the first few weeks are extremely important, and often that is the time where the woman does not even know if she is pregnant yet. A heart is beating by the time she finds out!
Obviously, alcohol and smoking anything can have adverse affects such as fetal alcohol syndrome. Any use of other drugs legal and illegal can obviously have a big impact. But our society and media, bought by the large pharmaceutical companies, keeps most women in the dark about how steroids (aka "birth control") also cause countless birth defects in the first few weeks of pregnancy - especially to male babies in utero..
A huge second source of birth defects are all the premature births needlessly caused because of a woman's previous abortion:
http://www.jpands.org/vol8no2/rooney.pdf
And, naturally, children born to early due his or her mother's compromised cervix and/or damaged uterus suffer from any number of birth defects as a result - the most common apparently being cerebral palsy.
These are the facts that big pharma and planned parenthood are doing their level best to keep everyone in the dark about, since these facts would not be good for their profits.