Effects of Prenatal Gabapentin Exposure on Fetal Skeletal Development in Rats: Assessment of Bone Development and Ossification

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Değermenci M., Uçar İ., Yılmaz S., Balcıoğlu E., Önder G. Ö., Unur E.

CYPRUS JOURNAL OF MEDICAL SCIENCES, cilt.11, sa.3, ss.202-209, 2026 (ESCI, TRDizin)

Özet

BACKGROUND/AIMS: Gabapentin (GBP) is often prescribed to pregnant women to manage neuropathic pain and epilepsy. However, the impact of antiepileptic drugs on prenatal skeletal development remains controversial. The aim of this study was to investigate, using a rat model, the possible toxic effects of GBP exposure during pregnancy on fetal bone development.

MATERIALS AND METHODS: Pregnant Wistar albino rats were randomly assigned to five groups (n=4 each): a control group and four GBPtreated groups receiving 10, 30, 60, or 120 mg/kg/day throughout gestation. Fetuses were collected at term and evaluated using double staining. Ossification lengths and areas of forelimb and hindlimb long bones were quantitatively measured. Immunohistochemical (IHC) analyses were performed on femoral sections to assess the distribution and staining intensity of alkaline phosphatase (AP) and tartrate-resistant acid phosphatase (TRAP), key markers of osteoblastic and osteoclastic activity, respectively.

RESULTS: Fetuses exposed to GBP demonstrated reduced body weight and smaller morphometric measurements compared with controls. Quantitative analysis revealed a significant decrease in ossification of both forelimb and hindlimb bones across all treatment groups, with a clear dose-dependent pattern. IHC findings showed diminished AP and TRAP immunoreactivity in GBP-exposed pups, indicating impaired bone formation and resorption .

CONCLUSION: Continuous GBP exposure during pregnancy adversely affects fetal skeletal development in rats. Prenatal GBP administration led to lower birth weight, delayed and reduced ossification, and suppressed bone metabolic activity, particularly at higher doses. We believe these findings highlight the potential developmental risks associated with GBP use during pregnancy and underscore the need for caution.