Neurodevelopment of children exposed in utero to phenytoin and carbamazepine monotherapy

D. Scolnik, I. Nulman, J. Rovet, D. Gladstone, D. Czuchta, H. A. Gardner, R. Gladstone, P. Ashby, R. Weksberg, T. Einarson and al. et
Motherisk Program, Hospital for Sick Children, Toronto, Ontario, Canada.

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.

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