Growth failure, tardive dyskinesia, megacolon development, and hepatic damage in neonatal rats following exposure to trimethobenzamide in utero

Abstract

Objective. Trimethobenzamide (TMB) has a pregnancy category C labeling. Tardive dyskinesia and gastrointestinal involvement in neonates were not described earlier. We aimed to investigate neurological, developmental, and hepatic effects of TMB.

Methods. Ten 10 pregnant rats were divided into two groups. During pregnancy, Group I (control) were injected with saline; Group II with TMB (5 mg/kg/day). After delivery, two experiments were planned: experiment 1 (neuro) and Experiment 2 (hepatic). Control groups contained offsprings delivered from Group I mothers: Group I-offsp-neuro (n = 15) and Group I-offsp-hepatic (n = 15). Thirty offsprings delivered from Group II mothers formed Group II-offsp-neuro (n = 15) and Group II-offsp-hepatic (n = 15). Neuro group offsprings were followed-up to observe neurological symptoms and assessed for normal growth. Hepatic group livers were excised for histological evaluation.

Results. The body weight between neuro groups showed significant differences (p < 0.05). In Group II-offsp-neuro low body weight, poor hair growth, tardive dyskinesia and megacolon were observed. Some alterations of liver histology were noticed in Group II-offsp-hepatic (p < 0.001).

Conclusions. In utero TMB exposure may cause growth retardation, neurological damage in the developing brain and intestine, and hepatic damage. Despite recent publications reporting safety of TMB, we suggest that obstetricians and pediatricians should make a good risk–benefit assessment before prescribing TMB.

Keywords:

• Trimethobenzamide
• growth failure
• tardive dyskinesia
• megacolon
• histopathology
• liver
• pregnancy
• rat

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.