Interpretation of controversial teratogenic findings of drugs such as phenobarbital.

Objective. To check the debated association between phenobarbital treatment during pregnancy and risk for congenital abnormalities (CAs) in their children. Study Design. It is a comparison of phenobarbital treatment in the mothers of cases with CA and matched controls without CAs in the Hungarian Case-Control Surveillance System of Congenital Abnormalities. Results. Of 22,843 cases with CA, 149 (0.65%) had mothers with phenobarbital treatment, while of 38,151 control newborn infants without CA, 209 (0.55%) were born to mothers with phenobarbital treatment (100-400 mg daily) (OR with 95% CI : 1.3, 1.1-1.7). Of 16 CA groups, only hypospadias had a higher risk after phenobarbital treatment in the critical period of this CA (OR with 95% CI : 2.4, 1.1-5.4). However, if only medically recorded phenobarbital treatments were evaluated and multiple testing bias was considered, this association would disappear. Conclusions. This study stresses the importance of the exclusion of recall bias and multiple testing bias.