Effect of maternal fluoxetine administration on uterine blood flow, fetal blood gas status, and growth.
Clinical depression, diagnosed in 5-15% of women during pregnancy, increases the risk of negative pregnancy outcomes including an increased incidence of low birth weight newborns and preterm delivery. Fluoxetine, a selective serotonin reuptake inhibitor, is often prescribed to treat depression due to its efficacy, high margin of safety, and mild side effects. However, fluoxetine initially increases plasma serotonin concentration, and serotonin causes uterine vasoconstriction in sheep, which could result in fetal hypoxemia. To assess fetal fluoxetine effects, late-gestation pregnant sheep were surgically prepared for the measurement of blood gases, heart rate, blood pressure, and uterine artery blood flow (n = 29). Ewes received a 70-mg bolus i.v. infusion of fluoxetine over 2 min in 10 mL of sterile water followed by continuous infusion at a rate of 100 microg/min for 8 d (n = 14), or continuous infusion of sterile water (n = 15). Transient decreases in uterine artery blood flow, fetal PO(2), and oxygen saturation were observed within the first 15 min after fluoxetine exposure, which did not return to normal values by 24 h. Fetal pH decreased and PCO(2) increased over the first 4 h with a return to normal by 24 h. However, there were no differences in uterine artery blood flow, blood gas status, or cardiovascular measures between the control and fluoxetine group over the rest of the 8-d infusion period. Thus, fluoxetine exposure during pregnancy has transient effects on fetal status that may be of developmental consequence if they occur repetitively.
Morrison
Janna Leigh
JL
Department of Obstetrics and Gynaecology, British Columbia Research Institute for Children's & Women's Health, Vancouver, BC, Canada.
Chien
Caly
C
Riggs
Kenneth Wayne
KW
Gruber
Nancy
N
Rurak
Dan
D
D000136:Acid-Base Equilibrium; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001784:Blood Gas Analysis; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D003863:Depression / Q000188:drug therapy; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D005333:Fetus / Q000187:drug effects* / Q000502:physiology; D005473:Fluoxetine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006339:Heart Rate; D006801:Humans; D019344:Lactic Acid / Q000097:blood; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy; D011256:Pregnancy Outcome; D012039:Regional Blood Flow / Q000187:drug effects; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D012756:Sheep; D014599:Uterus / Q000098:blood supply*
D018687:Antidepressive Agents, Second-Generation; D001786:Blood Glucose; D005473:Fluoxetine; D019344:Lactic Acid; D017367:Selective Serotonin Reuptake Inhibitors