Birth defects affect 1 in 33 newborns. Severe neural tube defects, such as anencephaly and spina bifida, affect about 1 in 1000.
Anti-Epileptic Drugs. Maternal valproic acid use while pregnant was associated with a 9.8x risk of neural tube defects, and carbamazepine use during pregnancy was associated with a 5x risk of neural tube defects.
Alcohol. This could be a very big topic, but for example, one study found that mothers who drank heavily had a 4.6x risk of birth defects. Fetal alcohol syndrome is usually found in children of women who had four or more drinks per day. 
Folic Acid Deficiency. In a randomized study of 1875 women who had a previous pregnancy with a birth defect, women who were assigned placebo had a 3.6x risk of neural tube defects compared to those who were given a folic acid supplement. The prevalence of neural tube defects declined 19% after the food supply was fortified with folic acid in the 90’s. In particular, it’s important to have enough folic acid around the time of conception.
Diabetes. Having diabetes before pregnancy increases the rate of birth defects to 3.5-5.3x baseline. These are severe birth defects, like spina bifida, hydrocephaly, limb deficiency, renal agenesis — where whole organs are missing or nonfunctional. Pregestational diabetes was associated with about 50% of the birth defect categories analyzed.
Low B12. Women with low vitamin B12 levels during pregnancy had a 2.9x risk of neural tube defects.
Low Choline. Women in the bottom decile of choline levels had a 2.4x risk of neural tube defects compared to baseline, and women in the top decile had an 0.14x risk of neural tube defects, in a prospective study of more than 180,000 pregnant women.
Opioid Use. Maternal opioid use during pregnancy was associated with a 2.0x -2.7x risk of birth defects such as spina bifida or cardiac septal defects, in the large case-control National Birth Defects Prevention study.
Maternal Hyperthermia. Most studies in this meta-analysis looked at fever, but heated blankets, hot tubs, and saunas were also included; women who were exposed to high body temperatures while pregnant had a 2.0x risk of having fetuses with neural tube defects. A prospective study found that only high fevers during the critical period for neural tube closure around the first month of pregnancy, but not at other times during pregnancy, had higher risk of neural tube defects , suggesting that maternal fever is a teratogen.
Maternal smoking has a significant but smaller effect (1.0-1.2x risk) on birth defects.
I’ll leave till later a more detailed discussion of medications and environmental contaminants that can cause birth defects, because there are a lot of them.
The basic bottom lines seem to be:
- Take folic acid. No, really, it makes a big difference. Take it as soon as you start trying for a baby.
- Maybe also take B12 and choline.
- Don’t drink.
- Avoid diabetes.
- Avoid opioids. Don’t take valproic acid or carbamazapine.
- Get your flu shot, and generally try to stay away from febrile infections.
Correa, Adolfo, et al. “Diabetes mellitus and birth defects.” American journal of obstetrics and gynecology 199.3 (2008): 237-e1.
Broussard, Cheryl S., et al. “Maternal treatment with opioid analgesics and risk for birth defects.” American journal of obstetrics and gynecology 204.4 (2011): 314-e1.
MRC Vitamin Study Research Group. “Prevention of neural tube defects: results of the Medical Research Council Vitamin Study.” The lancet 338.8760 (1991): 131-137.
Honein, Margaret A., et al. “Impact of folic acid fortification of the US food supply on the occurrence of neural tube defects.” Jama 285.23 (2001): 2981-2986.
Moretti, Myla E., et al. “Maternal hyperthermia and the risk for neural tube defects in offspring: systematic review and meta-analysis.” Epidemiology16.2 (2005): 216-219.
Chambers, Christina D., et al. “Maternal fever and birth outcome: a prospective study.” Teratology 58.6 (1998): 251-257.
Hackshaw, Allan, Charles Rodeck, and Sadie Boniface. “Maternal smoking in pregnancy and birth defects: a systematic review based on 173 687 malformed cases and 11.7 million controls.” Human reproduction update(2011): dmr022.
O’Leary, Colleen M., et al. “Prenatal alcohol exposure and risk of birth defects.” Pediatrics 126.4 (2010): e843-e850.
Yaffe, Sumner J. (2011). Drugs in pregnancy and lactation : a reference guide to fetal and neonatal risk (9 ed.). Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. p. 527
Ray, Joel G., et al. “Vitamin B12 and the risk of neural tube defects in a folic-acid-fortified population.” Epidemiology 18.3 (2007): 362-366.