title: The teratogenicity of anticonvulsant drugs.
abstract: BACKGROUND
  The frequency of major malformations, growth retardation, and hypoplasia of the midface and fingers, known as the anticonvulsant embryopathy, is increased in infants exposed to anticonvulsant drugs in utero. However, whether the abnormalities are caused by the maternal epilepsy itself or by exposure to anticonvulsant drugs is not known.
  
  
  METHODS
  We screened 128,049 pregnant women at delivery to identify three groups of infants: those exposed to anticonvulsant drugs, those unexposed to anticonvulsant drugs but with a maternal history of seizures, and those unexposed to anticonvulsant drugs with no maternal history of seizures (control group). The infants were examined systematically for the presence of major malformations, signs of hypoplasia of the midface and fingers, microcephaly, and small body size.
  
  
  RESULTS
  The combined frequency of anticonvulsant embryopathy was higher in 223 infants exposed to one anticonvulsant drug than in 508 control infants (20.6 percent vs. 8.5 percent; odds ratio, 2.8; 95 percent confidence interval, 1.1 to 9.7). The frequency was also higher in 93 infants exposed to two or more anticonvulsant drugs than in the controls (28.0 percent vs. 8.5 percent; odds ratio, 4.2; 95 percent confidence interval, 1.1 to 5.1). The 98 infants whose mothers had a history of epilepsy but took no anticonvulsant drugs during the pregnancy did not have a higher frequency of those abnormalities than the control infants.
  
  
  CONCLUSIONS
  A distinctive pattern of physical abnormalities in infants of mothers with epilepsy is associated with the use of anticonvulsant drugs during pregnancy, rather than with epilepsy itself.
authors: Pediatric Service, Massachusetts General Hospital, Boston 02114-2696, USA. holmes.lewis@mgh.harvard.edu
authors: L B
authors: LB
authors: Holmes
authors: E A
authors: EA
authors: Harvey
authors: B A
authors: BA
authors: Coull
authors: K B
authors: KB
authors: Huntington
authors: S
authors: S
authors: Khoshbin
authors: A M
authors: AM
authors: Hayes
authors: L M
authors: LM
authors: Ryan
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000453:epidemiology / Q000209:etiology*; D000927:Anticonvulsants / Q000009:adverse effects*; D002220:Carbamazepine / Q000009:adverse effects; D016022:Case-Control Studies; D000013:Congenital Abnormalities / Q000453:epidemiology / Q000209:etiology; D004827:Epilepsy / Q000188:drug therapy*; D005145:Face / Q000002:abnormalities; D005260:Female; D005317:Fetal Growth Retardation / Q000139:chemically induced; D005385:Fingers / Q000002:abnormalities; D006801:Humans; D007231:Infant, Newborn; D016015:Logistic Models; D010634:Phenobarbital / Q000009:adverse effects; D010672:Phenytoin / Q000009:adverse effects; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy*; D014635:Valproic Acid / Q000009:adverse effects
chemical_list: D000927:Anticonvulsants; D002220:Carbamazepine; D014635:Valproic Acid; D010672:Phenytoin; D010634:Phenobarbital