A pilot study of the teratogenicity of vagus nerve stimulation in a rabbit model

Abstract

Vagus nerve stimulation (VNS) is approved for the adjunctive treatment of both refractory epilepsy and treatment-resistant depression. This study assessed the effect of VNS on fertility, teratogenicity, and neonatal morbidity in rabbits. Ten female New Zealand white rabbits (test animals) were implanted with the VNS device. Ten additional female rabbits (surgical controls) received nonfunctional devices. Four additional female rabbits served as untreated controls and 10 male rabbits served for siring purposes. Test rabbits received VNS at 1 mA, 30 Hz, 500 microseconds, 30 seconds ON, 5 minutes OFF. Rabbits mated and were randomly assigned into 2 groups: those killed on day 28 and those proceeding through parturition. Groups were compared by using a 1-way analysis of variance with a Newman-Keuls Multiple Comparison post-hoc test. Differences between control and test animals were considered statistically significant if P </= .05. No statistically significant differences were noted for weight, matings required for successful copulation, food or water consumption, hematology, clinical chemistry, organ weights, uterine contents, kit weights and survival, or clinical observations. No changes or abnormalities could be attributed to the VNS device at necropsy or histopathologic assessment. No skeletal or soft tissue abnormalities were noted in any of the fetuses. In this very small sample of rabbits treated with VNS, we failed to find any conclusive teratogenic effects of VNS. The sample was too small, however, to support definitive conclusions regarding this issue. Brain stimulation devices in general and VNS in particular are potentially attractive in managing brain disorders such as epilepsy and depression during pregnancy and lactation as they do not have the systemic effects characteristic of medications and do not directly affect the fetus. Further studies are needed to address this issue.