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.