Intrauterine growth in the offspring of epileptic women: a prospective multicenter study

The aim of the present study was to evaluate the risk of intrauterine growt h delay in the offspring of epileptic mothers and to quantify the risks of intrauterine exposure to antiepileptic drugs (AEDs). Data concerning 870 ne wborns, prospectively collected in Canada, Japan and Italy, using the same study design, were pooled and analyzed. The overall proportion of newborns whose body weight (7.8%) or head circumference (11.1%) at birth were below the 10th percentile was not increased. However, logistic regression analysi s showed that the risk of small head circumference was significantly higher in Italian than in Japanese (RR 4.2; 95% CI: 2.2-8.0) or Canadian children (RR 2.6; 95% CI: 1.1-6.5), and in children exposed to polytherapy (RR 2.7; 95% CI: 1.2-6.3), phenobarbital (PB) (RR 3.6; 95% CI: 1.4-9.4) and primido ne (PRM) (RR 4.5; 95% CI: 1.5-13.8). Country was also the only factor affec ting low body weight, with Italian children having a higher risk than Japan ese (RR 5.2; 95% CI: 2.6-10.4) or Canadian (RR 8.8; 95% CI: 2.0-38.1) child ren. Due to the small categories, the influence of AED doses and plasma con centrations was studied for each individual AED, without adjustment for the other potential confounding factors. A clear dose-dependent effect was fou nd for PB and PRM in terms of both small head circumference and low body we ight, and a concentration-dependent effect for PB in terms of small head ci rcumferences. The size of the difference between the Italian and the other two populations, which is only partially explained by differences in therap eutic regimens, suggests that genetic, environmental and ethnic factors als o need to be taken into account when considering possible explanations. (C) 1999 Elsevier Science B.V. All rights reserved.