Abstract

Selective serotonin reuptake inhibitors (SSRI) are the most commonly prescribed drug class in the US. Untreated depression during pregnancy creates a risk for maternal wellbeing and is coupled with adverse pregnancy outcomes with causes that are poorly understood and use of SSRI among pregnant women is increasing. Fluoxetine (Prozac) and sertraline (Zoloft) are the most prescribed medications for pregnant women in their first trimester. With nearly one in five women experiencing depression, SSRI use during pregnancy continues to increase in the US. Antenatal SSRI use has been demonstrated to also result in increased neonatal mortality and morbidity. Therefore, presenting a conundrum for medical care providers when making decisions as to how to treat pregnant women with depression and also protect the pregnancy, and health outcomes for the infant. Importantly, and often under looked, is that SSRI not only impact the neuronal serotonin transporter (SERT), but they also impact the effects of SERT throughout the body. Our work has recently demonstrated that treatment with fluoxetine prepartum results increased death of offspring and increased morbidity for the offspring that survive, which we have recapitulated in a sheep model. Further, our work demonstrates the SSRI also impact both mammary gland function and development, as well as maternal outcomes, recently demonstrating that use of fluoxetine increases adiposity in offspring up to 12 weeks of age, and that male offspring appear to be disproportionally affected. We continue to investigate the impact of SSRI use on the placenta, mammary gland development, and long-term effects on both dam and offspring. Our goal is to develop novel interventions that will allow the dam to continue SSRI treatment if needed that will not impact her long-term health, as well as the long-term health of the offspring.