Sildenafil may help treat PH in newborns at high altitudes
Clinical observations support extending medication's indications to newborns
Sildenafil — a medication that relaxes blood vessels, thereby increasing blood flow — may possibly be used to treat neonatal pulmonary hypertension in babies born at high altitudes, where less oxygen is available for breathing.
This is according to clinical observations by Alexandra Heath-Freudenthal, MD, a pediatric cardiologist, while providing care in the Bolivian cities of La Paz and El Alto, located more than 2.2 miles above sea level on the Andes mountains in South America.
While the observations are preliminary, they may provide ground for extending the indication of sildenafil, approved under the brand names Revatio and Liqrev for patients with pulmonary arterial hypertension, to newborns.
“With further research, and after establishing risk-to-benefit ratios, we might have another option for these babies at high altitude and be able to give them the opportunity for a better outcome,” Colleen Julian, PhD, an associate professor at the University of Colorado School of Medicine in Aurora, said in a university news story.
‘Natural laboratory’ to study effects of low oxygen on pregnancy
Julian travels regularly to high-altitude locations, “a natural laboratory to study the effects of hypoxia [low oxygen] on physiological adaptation to pregnancy and maternal-infant health outcomes.”
The clinical observations were mentioned in “Surviving birth at high altitude,” which was published as a symposium review in The Journal of Physiology.
Air at high altitudes has fewer gas molecules than air that’s closer to sea level. This can limit how much oxygen gets to a baby developing in the mother’s womb, and can cause serious problems like preeclampsia (a sudden increase in blood pressure after 20 weeks of pregnancy) and other conditions marked by hypertension, or high blood pressure.
While such conditions increase the risk of complications for both mothers and their babies, including neonatal pulmonary hypertension and slow growth during early infancy, much about their underlying mechanisms and therapeutic options remains unknown.
“This makes it critical to focus research efforts on identifying the mechanisms involved in these conditions, potential therapeutic avenues, and ways to identify high-risk pregnancies as early as possible,” Julian said.
“Effective therapies for these conditions simply don’t exist,” she added. “The only cure for preeclampsia is early delivery of the baby, which is far from ideal and, depending on the timing, can have devastating consequences for the newborn.”
Some preterm babies with PH responded well to Revatio
In pulmonary hypertension, sildenafil relaxes the blood vessels in the lungs and lowers blood pressure, easing symptoms. Earlier work showed some preterm babies with pulmonary hypertension respond well to Revatio, given as a continuous infusion into the blood.
This is in line with Heath-Freudenthal’s own clinical observations that sildenafil may help a developing baby get enough oxygen, or at least shorten the time the baby needs extra oxygen support. This could help reduce infant deaths at high altitudes.
“By integrating our recent scientific and clinical observations in Bolivia with existing literature, we propose potential avenues to reduce the infant mortality burden at high altitudes and reduce pulmonary vascular disease in highland neonates,” the researchers wrote.
However, more research needs to be done to understand how sildenafil works.
“The next step would be to design a trial to quantitively determine whether it does improve outcomes or reduces the amount of time a baby has to be on oxygen,” Julian said. “In addition, populations of lowland and highland ancestry live across a wide gradient of altitude, so we can begin to dissect the interactive and independent effects of genes and hypoxia on physiological responses to pregnancy and pregnancy outcomes.”
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