Statins could stop accelerated aging among premature babies, study reveals
CAMBRIDGE, UK — Statins may hold the key to saving the lives of premature babies, who can age faster than other children. University of Cambridge researchers say the cholesterol-lowering drugs may also reduce the risk of cardiovascular problems in newborns. Experiments in rats suggest that doctors should administer these drugs in combination with steroids — the gold standard treatment for preterm babies.
Doctors often give babies born before 37 weeks gestation drugs called glucoticoids. However, researchers say these steroids have potentially deadly side effects on a child’s heart. Statins reduce the risk, the team says.
“Our discovery suggests that combined glucocorticoid and statin therapy may be safer than glucocorticoids alone in the treatment of preterm infants,” says lead author Professor Dino Giussani from the University of Cambridge in a press release.
“We are not saying to stop using glucocorticoids as they are clearly a life-saving treatment. We say that to improve this therapy – to fine-tune it – we could combine it with statins,” continues Prof. Giussani.
“This gives us the best of both worlds – we can maintain the benefits of steroids on the developing lungs, but ‘stamp out’ their adverse side effects on the developing heart and circulatory system, making the therapy much safer for treating preterm births.” .”
In rodent pups, the developmental airway benefits persisted, while any problems were “screened out” by the statins. The Cambridge team plans to replicate the test in sheep, which have similar physiology to humans, before conducting clinical trials in children.
Premature birth can lead to serious health problems
According to the Centers for Disease Control and Prevention, about one in ten children in the United States is born prematurely. Scientists suspect rising rates of obesity and type 2 diabetes may be behind the rise. Globally, up to 40 percent of children in low-income countries are born prematurely.
Premature birth increases the risk that newborns will die or develop health problems that can last a lifetime. Premature babies are extremely vulnerable because they miss a crucial final stage of development. The hormone cortisol is produced and released exponentially into the blood of the unborn baby. Cortisol is crucial for the maturation of organs and systems needed to keep the baby alive after birth. In the lungs, for example, cortisol makes them more elastic. This allows the lungs to expand to allow the baby to take its first breath. Without cortisol, a newborn’s lungs would be too stiff, leading to respiratory distress syndrome (RIS) – which could be fatal.
Glucocorticoid therapy is the established treatment given to the mother before birth or directly to the baby after birth. The synthetic steroids mimic natural cortisol by speeding up the development of organs – including the lungs – meaning the preterm baby is much more likely to survive. However, they can lead to a phenomenon known as “accelerated aging.”
“Glucocorticoids are a definite lifesaver, but the problem with steroids is that they speed up the maturation of all organs. This is good for the baby’s lungs, but it can be harmful to the heart and circulatory system – it is like accelerated aging,” adds the researcher from the Department of Physiology, Development and Neuroscience.
Why are steroids so harmful?
According to the team’s release, lab member Dr. Andrew Kane that this could be due to steroids causing oxidative stress. Steroids create an imbalance of molecules known as free radicals, resulting in a decrease in nitric oxide.
Nitric Oxide is very beneficial for the cardiovascular system. It increases blood flow and has antioxidant and anti-inflammatory properties. A previous clinical study by Oxford University researchers found that those exposed to glucocorticoid therapy via their mothers as unborn babies showed signs of cardiovascular health typical of people a decade older.
Therefore, Prof. Giussani and the team combined steroid treatment with statins, which are commonly used to lower cholesterol and are known to increase nitric oxide. They gave rat pups the synthetic steroid dexamethasone in combination with the statin pravastatin.
Two other groups received dexamethasone or pravastatin alone, while a control group received saline only. The team took measurements of respiratory and cardiovascular function when the rats reached ‘childhood’ age. As expected, steroids had adverse effects on the heart and blood vessels. There were also molecular signs of cardiovascular problems.
However, when the rats received statins at the same time, the rats received some protection. Crucially, the statins did not affect any of the beneficial effects of steroids on the respiratory system.
The results are published in the journal hypertension.
Mark Waghorn, author of South West News Servicer, contributed to this report.