The correlation of deficits in IQ with midface and digit hypoplasia in children exposed in utero to anticonvulsant drugs.
OBJECTIVE
Children exposed during pregnancy to the anticonvulsant drugs phenytoin, phenobarbital, and carbamazepine as monotherapy and polytherapy have an increased frequency of midface and digit hypoplasia. Some children also have cognitive dysfunction. The hypothesis tested is that the anticonvulsant drug-exposed child with midface and digit hypoplasia is more likely to have cognitive dysfunction.


METHODS
Children exposed to anticonvulsant drugs (n = 80) were recruited for a follow-up evaluation, which included testing cognitive function and a physical examination for head size, height, and the presence of midface and digit hypoplasia. Microcephaly, midface and digit hypoplasia, and major malformations were correlated with full scale (FSI), performance (PIQ) and verbal (VIQ) intelligence.


RESULTS
The presence of the 3 anticonvulsant-exposed children with microcephaly had a deficit of 23.7 IQ points in FSI in comparison with the other children with a normal head size. Either midface or digit hypoplasia, after excluding the persons with microcephaly and with the Bonferroni correction, correlated significantly with deficits in VIQ (-12.7), PIQ (-10) and FSI (-12.8) IQ points ( P = .0061). There was no decrease in IQ in association with major malformations.


CONCLUSIONS
The presence of midface and digit hypoplasia in a child exposed to anticonvulsant drugs in pregnancy is an indication for a systematic developmental evaluation.
Holmes
Lewis B
LB
Genetics and Teratology Unit, Massachusetts General Hospital, Boston, MA 02115, USA. holmes.lewis@mgh.harvard.edu
Coull
Brent A
BA
Dorfman
Jon
J
Rosenberger
Peter B
PB
D000014:Abnormalities, Drug-Induced; D000927:Anticonvulsants / Q000009:adverse effects*; D002220:Carbamazepine / Q000009:adverse effects; D002648:Child; D003072:Cognition Disorders / Q000139:chemically induced*; D005145:Face / Q000002:abnormalities*; D019066:Facies; D005260:Female; D005385:Fingers / Q000002:abnormalities*; D005500:Follow-Up Studies; D006801:Humans; D007361:Intelligence Tests; D010634:Phenobarbital / Q000009:adverse effects; D010672:Phenytoin / Q000009:adverse effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012307:Risk Factors; D014034:Toes / Q000002:abnormalities*
D000927:Anticonvulsants; D002220:Carbamazepine; D010672:Phenytoin; D010634:Phenobarbital