Drug treatment during pregnancy and isolated orofacial clefts in Hungary

Objective: To evaluate the possible association between all kinds of drug treatments during pregnancy and isolated cleft lip with or without cleft palate (CUP) and posterior cleft palate (PCP) in the offspring. Setting: The dataset of the large population-based Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996, was evaluated. Participants: One thousand three hundred seventy-four cases with isolated CUP and 601 with PCP, plus 38,151 population controls (without birth defects) and 20,868 malformed controls with other defects. Intervention: In this observation case-control study the data collection was based on prospective medical records particularly prenatal logbook, retrospective maternal data via a self-reported questionnaire, and home visits of nonresponding mothers. Main outcome measures: Isolated CUP and PCP associated with drug treatments during pregnancy. Results: An increased risk for isolated CUP was found in cases born to mothers treated with amoxicillin, phenytoin, oxprenolol, and thiethylperazine during the second and third month of pregnancy, i.e., the critical period of isolated CUP. Risk of isolated PCP was increased in mothers with oxytetracycline and carbamazepine treatment during the third and fourth month of pregnancy, i.e., the critical period of PCR Conclusions: This study confirmed the orofacial cleft (OFC) inducing effect of phenytoin, carbamazepine, oxytetracycline, and thiethylperazine and suggested a possible association between OFCs and oxprenolol and amoxicillin. However, drugs may have only a limited role in the origin of isolated OFCs.