Aripiprazole is used to treat major psychotic disorders. Data on its pregnancy-related side effects is limited. The study aimed to evaluate the teratogenicity of maternal exposure to aripiprazole on embryo-lethality, growth, and development of rat fetuses. Pregnant rats were divided into control, low dose (LD), high dose (HD), and double high dose (DHD) aripiprazole groups receiving the drug from day 6 to 19 of gestation. On day 20, animals were sacrificed, and the number of implantations, resorptions, dead and alive fetuses, placental weight and diameter, umbilical cord length, and fetal growth parameters were recorded. Ponderal index and Crown rump length/Head length (CRL/HL) ratios were also calculated. Half of the fetuses were fixed randomly in Bouin’s solution. External and internal examinations were performed to detect congenital anomalies.
In the DHD group, measurements of the placentae, umbilical cords, and all the growth parameters of the fetuses were significantly reduced when compared to control and other treated groups (p<0.05). These reductions in parameters were less pronounced in the low and high therapeutic doses. A significant increase in embryo-lethality was observed exclusively in the DHD group. Very few anomalies were seen in DHD and HD groups. In conclusion, aripiprazole affects the growth of the fetuses in a dose-related manner due to histopathological changes in the placentae. The double high dose induced a severe remarkable symmetrical intrauterine growth restriction with a significant increase in embryo-lethality. Therefore, its use should be limited to therapeutic doses, avoiding higher doses due to their teratogenic effects.
