Findings in children exposed in utero to phenytoin and carbamazepine monotherapy: independent effects of epilepsy and medications

Abstract

Our objective was to evaluate the patterns of malformations in children exposed in utero to phenytoin (DPH) and carbamazepine (CBZ) monotherapy, and to compare them prospectively with matched mother-child pairs exposed to nonteratogens, and to separate the effects of antiepileptic drugs (AEDs) from those of epilepsy by collecting groups of untreated epileptics and those treated with DPH and CBZ for conditions other than epilepsy. This was a prospective, controlled, and blinded observational study. Thirty-six mother-child pairs exposed to CBZ monotherapy, 34 pairs exposed to DPH monotherapy, and 9 nonmedicated epileptic women and their children were compared with matched mother-child pairs exposed to nonteratogens. The control mothers were matched for maternal age, time of consultation, obstetric history, and socioeconomic status (SES). One main outcome measures a "blinded" morphological assessment of the offspring. We found that minor anomalies were significantly more common among children of epileptics on either drug (P = 0.01) and among DPH-treated nonepileptic offspring (P = 0.03). Among epileptics, the relative risk for minor anomalies following DPH (2.1) was similar to that after exposure to either DPH (P = 0.006) or CBZ (P = 0.01). Increased rates of hypertelorism were detected among DPH-exposed offspring. High forehead, frontal bossing, malar hypoplasia, epicanthus and micrognathia were associated with untreated epilepsy, as well as with DPH and CBZ treatment.