New research published today in the Journal of Physiology shows that giving sildenafil (Viagra), which cause blood vessels to dilate, impairs the fetus' ability to redirect blood flow to essential organs in response to low levels of oxygen, impeding fetal growth. This study was conducted in an animal model of growth restriction where placental blood flow is restricted.
It is well accepted that in a fetus, in response to low levels of oxygen throughout the body (called hypoxia) blood flow is redirected to essential organs (such as the brain and heart) and away from non-essential organs, to help sustain life.
This new finding about giving pregnant sheep Viagra was especially important because while this study was being conducted, a large clinical study was investigating maternal sildenafil in pregnancies affected by fetal growth restriction as a potential treatment to improve fetal growth and correct impaired placental function by increasing blood flow.
This clinical study was halted early, following evidence that maternal Viagra treatment resulted in increased morbidity in babies. However, the mechanisms behind the increased morbidity was not understood.
Our study provides crucial insight into a potential mechanism underlying the increased morbidity. We show that prenatal sildenafil lowered levels of oxygen in the fetal blood, but despite this, the fetus did not respond by redirecting blood to essential organs. This finding may underlie the adverse outcomes observed clinically.
Viagra is a well-known drug that dilates blood vessels and its ability to increase blood flow to certain areas has been well described in other medical conditions. Therefore, the investigation into its potential for improving fetal growth by increasing placental blood flow, was warranted.
However, we show that Viagra can cross the placenta and have effects on the fetus. The results of our study highlighted the importance of thorough pre-clinical investigation in large animal models prior to the initiation of large clinical trials.
Our study replicated the impaired placental function that was observed clinically, in fetal sheep as a pre-clinical model. Using sheep as a model organism, we were able to implant monitoring equipment into these fetal sheep to monitor changes in both maternal and fetal blood flow and physiology in response to low oxygen levels in the blood and Viagra treatment.
A key difference between our study and the previously discussed clinical trials, and a limitation, is the way we delivered the Viagra. Clinical studies involved oral administration to the mother, whereas we delivered sildenafil intravenously, which may have resulted in different circulating levels of the drug in the blood. Additionally, while our study demonstrates the effects of sildenafil in a growth restricted fetus, we could not investigate the effect of sildenafil on a healthy fetus.
First author Ishmael Inocencio said:
"A key finding of our study was the unexpected exacerbation of growth restriction following Viagra treatment. This has important implications for the danger of administering this drug to pregnant women."
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Journal
The Journal of Physiology