Maternal exposure to folic acid antagonists during pregnancy

Maternal exposure to medications known as folic acid antagonists appear to increase the risk of adverse outcomes of pregnancy due to their effects on the placenta (i.e. preeclampsia) as reported by Wen and others in the December 2, 2008 issue of the Canadian Medical Association Journal.

Previous studies have shown that folic acid antagonists when taken during pregnancy are associated with increased risks of neural tube defects (e.g. spina bifida), heart defects, cleft palate and defects of the urinary tract.

In the current study, the risks of preeclampsia, placental abruption, fetal growth restriction and fetal death were greater for mothers with exposure to folic acid antagonists within one year prior to delivery. The researchers reviewed the medical history of 14,982 women who had been exposed to a folic acid antagonists and compared them to 59,825 women who had not been exposed. The most common exposure was to sulfamethoxazole-trimethoprim (also known as TMP-sulfa or Bactrim) which is commonly used to treat urinary tract infections. Common folic acid antagonists are listed below.

As such, the authors state that this finding, combined with previous findings on the association between folic acid antagonists during pregnancy and birth defects should prompt a change in the FDA pregnancy category from C to D. Physicians who are caring from women of reproductive age, particularly those already pregnant and those with medical conditions and a high risk of unintended pregnancy, should use caution in prescribing folic acid antagonists and should perhaps consider alternative agents as first-line therapy...Patients who do take these medications might benefit from increased supplemental folic acid."

Commonly prescribed folic acid antagonists:
1. Antibiotic: trimethoprim
2. Anti-seizure medications: carbamazepine, phenytoin, phenobarbital, primidone
3. Anti-hypertensive: triamterene
4. Anti-cancer: methotrexate


References:
1. Maternal Exposures to folic acid antagonists appears to increase risk of placenta-mediated adverse pregnancy outcomes
2. Maternal exposure to folic acid antagonists and placenta-mediated adverse pregnancy outcomes (CMAJ 2008;179(12):1263-1268).
3. Folic Acid Antagonists during Pregnancy and the Risk of Birth Defects (N Engl J Med 2000;343:1608-14.)


For additional information on the importance of folic acid supplementation before and during pregnancy, click here.