Opioid-Induced Changes to Pregnancy Outcomes and Placental Structure in Rat Models

Maternal opioid-use disorder (MOUD) is a growing national health problem and the number of affected births quadrupled between 1999 and 2014.1 MOUD is correlated with abnormal placental trophoblast proliferation and villous vascularization, suggestive of chronic hypoxia and poor vascular integrity.2 Such damage to the placenta can be extremely disruptive, not only because of the placenta’s role in providing oxygen to the developing fetus, but also because of the placenta-brain axis, which modulates fetal brain development.3 MOUD may cause neurodevelopmental alterations via direct changes to the fetal brain or via indirect opioid-induced placental dysfunction which disrupts the placenta-brain axis. This study used a rat model of exposure to oxycodone, a commonly prescribed opioid; melatonin was also administered both separately and concurrently with oxycodone to assess its efficacy in reducing the adverse effects from oxycodone. Both oxycodone and melatonin treatments increased the relative area of the placental exchange region, called the labyrinth zone, but only melatonin had a significant impact on the fetal:placental weight ratio and fetal size. Thus, while melatonin increased placental efficiency by expanding the exchange area, the oxycodone-induced placental alterations did not increase placental efficiency. It is likely that these changes were necessary compensations for oxycodone-induced placental damage.