title: Association of prenatal phenobarbital and phenytoin exposure with small head size at birth and with learning problems.
abstract: Small head size has been observed in prenatally anticonvulsant-exposed neonates. In infancy, cognitive impairments were revealed. It is presently unknown 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 who had been included in the retrospective study. The retrospective study comprised 172 exposed and 168 control neonates, matched with respect to age, sex and their mothers' age. Prenatally phenobarbital + phenytoin-exposed neonates had a significantly smaller occipitofrontal circumference (OFC) than prenatally phenobarbital-monotherapy-exposed and control neonates (mean difference of 0.7 cm). In the follow-up, no difference in cognitive functioning was found between the exposed and the control groups. Most of the prenatally anticonvulsant-exposed subjects had normal intellectual capacity. However, 12% of the exposed subjects versus 1% of the controls had persistent learning problems. In addition, more of the exposed subjects were mentally retarded. 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 cognitive functioning in adulthood, but learning problems and mental retardation proved to be more prevalent among exposed subjects. Phenobarbital and phenytoin may therefore affect cognitive capacity but only in infants who are susceptible to this particular influence of the drugs.
authors.affiliation: Academic Medical Center, University of Amsterdam, Graduate School Neurosciences, The Netherlands.
authors.forename: A B
authors.initials: AB
authors.lastname: Dessens
authors.forename: P T
authors.initials: PT
authors.lastname: Cohen-Kettenis
authors.forename: G J
authors.initials: GJ
authors.lastname: Mellenbergh
authors.forename: J G
authors.initials: JG
authors.lastname: Koppe
authors.forename: N E
authors.initials: NE
authors.lastname: van De Poll
authors.forename: K
authors.initials: K
authors.lastname: Boer
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects*; D002508:Cephalometry; D003071:Cognition; D003430:Cross-Sectional Studies; D004827:Epilepsy / Q000188:drug therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007231:Infant, Newborn; D007360:Intelligence; D007859:Learning Disabilities / Q000209:etiology*; D008297:Male; D008568:Memory; D010634:Phenobarbital / Q000009:adverse effects*; D010672:Phenytoin / Q000009:adverse effects*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy; D011297:Prenatal Exposure Delayed Effects; D012189:Retrospective Studies
chemical_list: D000927:Anticonvulsants; D010672:Phenytoin; D010634:Phenobarbital