Folate-blocking drugs produce birth defects

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Drugs that interfere with the action of folic acid can produce a sharp increase in certain birth defects if taken during the first trimester of pregnancy, Israeli researchers reported today in the British Journal of Clinical Pharmacology. It is well-known that high levels of folate in pregnant women increase the chances of a healthy baby, and most medical authorities suggest that folate supplements be taken during pregnancy to minimize risks. Some previous studies have suggested that folate-blockers present a problem during pregnancy, but the new study is the largest ever to look at the issue, the authors said.

A team from Ben-Gurion University of the Negev studied 84,832 babies born at the Soroka Medical Center in Beer-Sheva. Most of the pregnant women were members of a large HMO that services southern Israel, and their medical records and prescriptions were available.

Epidemiologist Ilan Matok and his colleagues analyzed all the data, including therapeutic abortions, and concluded that use of the folate-blocking drugs more than doubled the risk of congenital malformations of the fetus, including neural tube, cardiovascular and urinary tract defects. The drugs increased the risk of spina bifida and malformations of the brain more than sixfold. The results are conservative, the researchers noted, because they were unable to include data about spontaneous abortions.

Among the drugs that cause problems are dihydrofolate reductase inhibitors, such as trimethoprim (Proloprim, Triprim and Monoprim), sulfasalazine (Azulfadine and Salazopyrin) and methotrexate that prevent folate from being converted into active metabolites. Other drugs that are known to lower serum and tissue concentrations of folate include the antiepileptic drugs -- such as carbamazepine (Tegretol, Carbatrol and others), phenytoin (Phenytek and Dilantin), lamotrigine (Lamictal), primidone, valproic acid (Depakote) and phenobarbital (Luminal) -- and cholestyramine (Questran and Cholybar). The antiepileptics are well-known for increasing the risk of birth defects, but not taking them can sometimes be even more hazardous to the prospective mother.

-- Thomas H. Maugh II