Growth failure, tardive dyskinesia, megacolon development, and hepatic damage in neonatal rats following exposure to trimethobenzamide in utero.
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.
Department of Medical Genetics, School of Medicine, Suleyman Demirel University, Isparta, Turkey. yasemin.goksu@gmail.com
Azize Yasemin
AY
Goksu Erol
Alpaslan
A
Gokcimen
Oner
O
Ozdemir
D000818:Animals; D000831:Animals, Newborn; D000932:Antiemetics / Q000009:adverse effects; D001549:Benzamides / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000473:pathology; D005260:Female; D006130:Growth Disorders / Q000139:chemically induced* / Q000473:pathology; D006627:Hirschsprung Disease / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects; D023421:Models, Animal; D009069:Movement Disorders / Q000209:etiology* / Q000473:pathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
D000932:Antiemetics; D001549:Benzamides; C100146:trimethobenzamide