Association of prenatal phenobarbital and phenytoin exposure with small head size at birth and with learning problems

Small head size has been observed in prenatally anticonvulsant-exposed neon ates. In infancy, cognitive impairments were revealed. It is presently unkn own whether these impairments are permanent or disappear after puberty. We studied the link between the prenatal influence of anticonvulsants on brain development and cognitive functioning in adulthood: a retrospective study on head size and a follow-up assessing cognitive capacities among adults wh o had been included in the retrospective study. The retrospective study com prised 172 exposed and 168 control neonates, matched with respect to age, s ex and their mothers' age. Prenatally phenobarbital + phenytoin-exposed neo nates had a significantly smaller occipitofrontal circumference (OFC) than prenatally phenobarbital-monotherapy-exposed and control neonates (mean dif ference of 0.7 cm). In the follow-up, no difference in cognitive functionin g was found between the exposed and the control groups. Most of the prenata lly anticonvulsant-exposed subjects had normal intellectual capacity. Howev er, 12% of the exposed subjects versus 1% of the controls had persistent le arning problems. In addition, more of the exposed subjects were mentally re tarded. There was no clear relationship between learning problems and small OFC, maternal epilepsy or unfavourable family climate. Conclusions: We conclude that the combination of phenobarbital + phenytoin affects the fetal OFC. The smaller OFC does not seem to be related to cogni tive functioning in adulthood, but learning problems and mental retardation proved to be more prevalent among exposed subjects. Phenobarbital and phen ytoin may therefore affect cognitive capacity but only in infants who are s usceptible to this particular influence of the drugs.