The use of antiepileptic drugs (AEDs) in children inhibits growth velocity, resulting in shorter stature, according to a study published in BMC Pediatrics.1 One year of treatment with common AEDs valproate and oxcarbazepine significantly decreased the rate of growth in 73 children diagnosed with epilepsy who were treated at the Tri-Service General Hospital of Taiwan Pediatrics Department.
The 40 boys and 33 girls, aged 1 to 18 years, were treated with valproate (n=23), oxcarbazepine (n=29) or a combination of both (n=21), and all were seizure-free for 6 months prior to the end of the evaluation period. General observations that AED treatment is associated with shorter stature in children have been attributed to immobility among many patients with severe epilepsy,2 however the authors enrolled only children who were ambulatory for the Taiwanese study.1 Participants were also subgrouped by age to account for normal changes in growth rates into pre-pubescent, pubescent, and postpubescent for analysis.
Two markers for bone growth were used: serum tartrate-resistant acid phosphatase 5b (TRAcP 5b) was used to measure bone resorption and serum bone-specific alkaline phosphatase (BAP) was used to measure bone formation. After 1 year of treatment with AEDs, mean activity of the bone resorption marker TRAcP 5b was 4.8 + 1.7 µmol/L/min, reflecting a decrease of standard deviation scores (SDS) of -1.6 + 1.2 µmol/L/min in the epileptic children, compared to normal age- and sex-matched controls. At the same time, there was an increase in activity of the bone formation marker BAP (SDS 1.7 + 3.7). There was no significant deviation from normal patterns of weight gain among children of the same age and sex.
Growth velocity slowed in the current study by a mean of -1.0 + 2.8/year from the pre-AED period to the post-AED period. Previous studies have observed disruption of the natural growth cycle in children taking various types of AEDs, with inconsistent results on measures of growth in stature.2,3 Investigation into impact of AEDs on growth velocity has been limited, and the underlying mechanisms have not been well understood.
Although there was a pattern of decreasing growth velocity among all the children in the study, this trend was most pronounced in early childhood (-1.4 + 3.3 cm/year) and less significant in puberty and post puberty (-0.7 + 2.6 cm/year, -0.7 + 1.8 cm/year respectively), when growth slows naturally.
Reductions in TRAcP 5b directly corresponded to increases in BAP, which was highly suggestive of increased bone turnover. These findings pointed to a potential role of uncoupling of bone metabolism underlying decreased growth velocity among children taking AEDs such as valproate and oxcarbazepine, even in the short term. The authors also pointed out that the study sample was relatively small, warranting larger-scale prospective investigation to substantiate their findings.
- Lin CM, Fan HC, Chao TL, et al. Potential effects of valproate and oxcarbazepine on growth velocity and bone metabolism in epileptic children—a medical center experience. BMC Pediatrics.2016;16:61.
- Guo CY, Ronen GM, Atkinson SA. Long-term valproate and lamotrigine treatment may be a marker for reduced growth and bone mass in children with epilepsy. Epilepsia. 2001;42(9):1141–7.
- Rattya J, Vainionpaa L, Knip M, et al. The effects of valproate, carbamazepine, and oxcarbazepine on growth and sexual maturation in girls with epilepsy. Pediatrics. 1999;103(3):588–93.