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Folic Acid
Title: Folic acid antagonists during pregnancy and the risk of birth defects
Author: S. Hernandez-Diaz, et al.
Address: Brookline, Massachusetts
Source: The New Englan Journal of Medicine 343:1608-1614 (November) 2000
Summary: Researchers wanted to determine if the folic acid component of multivitamins is responsible for the reduction in risk of cardiovascular defects, oral clefts and urinary tract defects in infants by examining the associations between maternal use of folic acid antagonists and these congenital malformations. They studied the exposure to folic acid antagonists that act as dihydrofolate reductase inhibitors and to certain antiepileptic drugs in 3870 infants with cardiovascular defects, 1962 infants with oral clefts, and 1100 infants with urinary tract defects. The control group consisted of 6249 infants with structural defects and 2138 infants with chromosomal or mendelian defects. The relative risks of cardiovascular defects and oral clefts in infants whose mothers were exposed to dihydrofolate reductase inhibitors during the second or third month after the last menstrual period, as compared with infants whose mothers had no such exposure, were 3.4 and 2.6 respectively. The relative risks of cardiovascular defects, oral clefts, and urinary tract defects after maternal exposure to antiepileptic drugs were 2.2, 2.5, and 2.5 respectively. Use of multivitamin supplements containing folic acid diminished the adverse effects of dihydrofolate reductase inhibitors, but not that of antiepileptic drugs. It was concluded that folic acid antagonists, which include such common drugs as trimethoprim, triamterene, carbamazepine, phenobarbital, and primidone, may increase the risk of neural-tube defects, as well as cardiovascular defects, oral clefts, and urinary defects. However, folic acid in multivitamins may reduce the risks of these defects.