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Intrauterine growth in the offspring of epileptic women: a prospective multicenter study
D Battino1, S Kaneko, E Andermann
1Carlo Besta Neurological Institute, Milan, Italy. dbattino.besta@interbusiness.it
Insights
Maternal epilepsy and antiepileptic drug (AED) exposure may affect fetal growth. Italian newborns had higher risks of low birth weight and small head circumference, with dose-dependent effects for certain AEDs.
Area of Science:
- Perinatal medicine
- Pharmacology
- Genetics
Background:
- Epilepsy in pregnant women necessitates careful management of antiepileptic drugs (AEDs).
- Intrauterine exposure to AEDs may pose risks to fetal development, including growth delay.
- Previous studies have indicated potential associations, but further quantification is needed.
Purpose of the Study:
- To evaluate the risk of intrauterine growth delay in offspring of epileptic mothers.
- To quantify the risks associated with intrauterine exposure to specific antiepileptic drugs (AEDs).
- To explore potential contributing factors, including country of birth and AED regimens.
Main Methods:
- Pooled analysis of prospectively collected data from 870 newborns across Canada, Japan, and Italy.
- Logistic regression analysis to assess the risk of low birth weight and small head circumference.
- Investigation of dose- and concentration-dependent effects for individual AEDs.
Main Results:
- Overall proportions of newborns below the 10th percentile for body weight or head circumference were not increased.
- Significantly higher risk of small head circumference in Italian newborns compared to Japanese or Canadian.
- Increased risk of low body weight in Italian newborns.
- Polytherapy, phenobarbital (PB), and primidone (PRM) were associated with higher risks of small head circumference.
- Dose-dependent effects observed for PB and PRM on head circumference and body weight; concentration-dependent effect for PB on head circumference.
Conclusions:
- While overall growth delay was not increased, specific risks exist for certain populations and AED exposures.
- Italian newborns exhibited higher risks for low body weight and small head circumference, suggesting multifactorial influences.
- Dose and concentration of AEDs, particularly PB and PRM, play a role in fetal growth parameters.
- Genetic, environmental, and ethnic factors likely contribute to observed population differences in fetal growth outcomes.
Abstract:
The aim of the present study was to evaluate the risk of intrauterine growth delay in the offspring of epileptic mothers and to quantify the risks of intrauterine exposure to antiepileptic drugs (AEDs). Data concerning 870 newborns, 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 analysis 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 primidone (PRM) (RR 4.5; 95% CI: 1.5-13.8). Country was also the only factor affecting low body weight, with Italian children having a higher risk than Japanese (RR 5.2; 95% CI: 2.6-10.4) or Canadian (RR 8.8; 95% CI: 2.0-38.1) children. Due to the small categories, the influence of AED doses and plasma concentrations was studied for each individual AED, without adjustment for the other potential confounding factors. A clear dose-dependent effect was found for PB and PRM in terms of both small head circumference and low body weight, and a concentration-dependent effect for PB in terms of small head circumferences. The size of the difference between the Italian and the other two populations, which is only partially explained by differences in therapeutic regimens, suggests that genetic, environmental and ethnic factors also need to be taken into account when considering possible explanations.
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