Neurodevelopment of Children Exposed in Utero to Phenytoin and Carbamazepine Monotherapy

JAMA. 1994 Mar 9;271(10):767-70.

Abstract

Objective: To compare pregnancy outcome prospectively after phenytoin and carbamazepine monotherapy with outcome in matched mother-child pairs exposed to nonteratogens to evaluate the relative fetal safety of these drugs.

Design: A prospective, controlled, and blinded observational study.

Patients: Thirty-six mother-child pairs exposed to carbamazepine monotherapy and 34 pairs exposed to phenytoin monotherapy, all prospectively studied, were compared with mother-child pairs exposed to nonteratogens. The controls were matched for maternal age, time of consultation, obstetric history, and socioeconomic status.

Main outcome measure: The primary end point of interest was the children's global IQ measured by either the Bayley or the McCarthy scale according to their ages.

Setting: A teratology consultation program and two neurology services in Toronto, Ontario.

Results: Children exposed to phenytoin in utero had a mean (+/- SD) global IQ 10 points lower (95% confidence interval, 4.9 to 15.8 points) than their matched controls (113.4 +/- 13.1 and 103.1 +/- 25.1; P = .038). The Reynell language development scores followed a similar trend, with children exposed to phenytoin scoring significantly lower than their controls. Phenytoin-exposed children had a global IQ of 84 or less significantly more often than the control group (P < .01). Children exposed in utero to carbamazepine did not differ from their controls on any of the neurobehavioral tests.

Conclusions: Our study suggests a clinically important negative effect of phenytoin on neurobehavioral development, independent of maternal or environmental factors, causing a substantial number of children to achieve a lower score than expected on cognitive tests. No similar effects could be shown after gestational use of carbamazepine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbamazepine / adverse effects*
  • Carbamazepine / therapeutic use
  • Case-Control Studies
  • Child
  • Cognition / drug effects*
  • Developmental Disabilities / chemically induced*
  • Female
  • Humans
  • Intelligence Tests
  • Male
  • Phenytoin / adverse effects*
  • Phenytoin / therapeutic use
  • Pregnancy
  • Pregnancy Complications / drug therapy
  • Pregnancy Outcome
  • Prenatal Exposure Delayed Effects*
  • Prospective Studies

Substances

  • Carbamazepine
  • Phenytoin