Effect of Low and High Doses of Two Selective Serotonin Reuptake Inhibitors on Pregnancy Outcomes and Neonatal Mortality

Abstract

Selective serotonin reuptake inhibitors (SSRI) are the most common antidepressant used by pregnant women; however, they have been associated with adverse pregnancy outcomes and perinatal morbidity in pregnant women and animal models. We investigated the effects of two SSRI, fluoxetine and sertraline, on pregnancy and neonatal outcomes in mice. Wild-type mice were treated daily with low and high doses of fluoxetine (2 and 20 mg/kg) and sertraline (10 and 20 mg/kg) from the day of detection of a vaginal plug until the end of lactation (21 days postpartum). Pregnancy rate was decreased only in the high dose of fluoxetine group. Maternal weight gain was reduced in the groups receiving the high dose of each drug. Number of pups born was decreased in the high dose of fluoxetine and low and high doses of sertraline while the number of pups weaned was decreased in all SSRI-treated groups corresponding to increased neonatal mortality in all SSRI-treated groups. In conclusion, there was a dose-dependent effect of SSRI on pregnancy and neonatal outcomes in a non-depressed mouse model. However, the distinct placental transfer of each drug suggests that the effects of SSRI on pup mortality may be mediated by SSRI-induced placental insufficiency rather than a direct toxic effect on neonatal development and mortality.

Keywords: fluoxetine; neonatal morbidity; perinatal mortality; selective serotonin reuptake inhibitor; sertraline.

Figure 1

Effect of fluoxetine (a,b) and sertraline (c–f) on maternal weight gain between days post coitum (DPC) 0.5 to 6.5 (a,c,e) using data from pregnant (before the effect of fetal weight on maternal weight), nonpregnant, and virgin mice. Maternal weight gain (b,d,f) during entire gestation (DPC 0.5 to 18.5) used data from only pregnant mice with data analyzed for DPC 7.5 to 18.5. * Indicates significantly decreased weight in the high dose of fluoxetine group.

Figure 2

Effect of fluoxetine (a–c) and sertraline (d–i) on neonatal outcomes: Number of pups born per litter (a,d,g); number of pups weaned per litter (b,e,h). Survival analysis of pup mortality (c,f,i) during lactation (days postpartum 0.5 to 21.5).

Figure 3

Maternal weight change between the last day of pregnancy and the day of parturition in the fluoxetine (a) and sertraline (b,c) studies. * Denotes dams that were euthanized after parturition and had fully developed dead pups in the uterus.