Medications that block folic acid in pregnancy double risk of congenital malformations in fetus

Pregnant women are advised to take vitamin supplements containing folic acid as part of their routine pre-natal care. Now, a new study warns that taking medications that reduce or block the actions of folic acid during the first trimester of pregnancy increase the risk that the growing baby will develop abnormalities. The large collaborative cohort study was conducted by researchers at Ben-Gurion University of the Negev. This conclusion just published in the British Journal of Clinical Pharmacology was reached by a team of epidemiologists, pediatricians, clinical pharmacologists, obstetricians and gynecologists who examined birth and abortion data collected in Israel between 1998 and 2007.

The study obtained medication data from pregnant mothers registered at Clalit HMO, Southern District, and drew information from 84,832 babies born at Soroka University Medical Center in Beer-Sheva, Israel. It was carried out as part of the Ph.D. dissertation of Ilan Matok, and supervised by principal investigators Dr. Amalia Levy and Prof. Rafael Gorodischer from Ben-Gurion University of the Negev in Israel, in collaboration with Prof. Gideon Koren from the Division of Clinical Pharmacology, Hospital for Sick Children in Toronto, Canada (the BeMORE collaboration).

"After studying the data, we concluded that first trimester exposure to folic acid antagonists is associated with increased risk for neural tube, cardiovascular and urinary tract defects," according to the pediatrician and clinical pharmacologist, principal investigator Dr. Rafael Gorodischer, professor emeritus at Ben-Gurion University of the Negev.

Healthcare professionals now encourage women to take folic acid supplements or eat food fortified with folic acid if they are planning to get pregnant, as well as during early pregnancy because there is clear evidence that this reduces the risk of any resulting baby having neural tube defects and possibly other birth defects (congenital malformations).

The team considered the effects of two groups of medications on pregnancy. Each group consists of drugs that prevent folic acid working in the body. One group (dihydrofolate reductase inhibitors) prevents folate from being converted into its active metabolites and includes trimethoprim (antibiotic), sulfasalazine (for ulcerative colitis) and methotrexate (chemotherapeutic). The other medications are known to lower serum and tissue concentrations of folate by various mechanisms, and include antiepileptics (carbamazepine, phenytoin, lamotrigine, primidone, valproic acid and phenobarbital) and cholestyramine (reduces cholesterol).

"The study shows that exposure to folic acid antagonists in the first trimester of pregnancy more than doubles the risk of congenital malformations in the fetus, and that neural tube defects, such as spina bifida and malformations of the brain, increase by more than six-fold after exposure to these antagonists," said Dr. Amalia Levy, an epidemiologist with the BGU Faculty of Health Sciences and chair of the BeMORE collaboration.

"Clinicians should try to avoid the use of these drugs whenever possible in women contemplating pregnancy," concluded Gorodischer.

Source: American Associates, Ben-Gurion University of the Negev