CAMBRIDGE, United Kingdom — Statins could hold the key to saving the lives of premature babies, who can age faster than other children. Researchers at the University of Cambridge say the cholesterol lowering drugs can also reduce the risk of cardiovascular problems in newborns. Experiments with rats suggest that doctors should administer these drugs in combination with steroids — the gold standard treatment for premature infants.
Doctors often give medications called glucocoticoids to babies delivered before 37 weeks of gestation. However, researchers say these steroids have potentially fatal side-effects on a child’s heart. Statins reduce the risk, according to the team.
“Our discovery suggests that combined glucocorticoid and statin therapy may be safer than glucocorticoids alone for the treatment of preterm babies,” says lead author Professor Dino Giussani from the University of Cambridge in a media release.
“We’re not saying to stop using glucocorticoids, as they are clearly a life-saving treatment. We’re saying that to improve this therapy – to fine tune it – we could combine it with statins,” Prof. Giussani continues.
“This gives us the best of both worlds – we can maintain the benefits of steroids on the developing lungs, but ‘weed out’ their adverse side-effects on the developing heart and circulation, thereby making therapy much safer for the treatment of preterm birth.”
In rodent pups, benefits on developing respiratory systems remained while any problems were “weeded out” by the statins. The Cambridge team plans to replicate the test in sheep, which have a similar physiology to humans, before conducting clinical trials with children.
Premature birth can lead to serious health problems
Approximately one in 10 children in the United States is born premature, according to the Centers for Disease Control and Prevention. Scientists suspect that rising rates of obesity and Type 2 diabetes may be behind this rise. Globally, up to 40 percent of children are born premature in low-income countries.
Premature birth increases the risk of newborns dying or developing health issues that may persist throughout their lives. Preterm babies are extremely vulnerable because they miss out on a crucial final developmental stage. This is when the hormone cortisol is produced and released exponentially into the unborn baby’s blood. Cortisol is vital to the maturation of organs and systems that are needed to keep the baby alive once born. For example, in the lungs, cortisol ensures that they become more elastic. This allows the lungs to expand so the baby can take its first breath. Without cortisol, a newborn’s lungs would be too stiff, which leads to respiratory distress syndrome (RDS) — which could be fatal.
Glucocorticoid therapy is the established treatment, given to the mother before the baby is born or directly to the baby after birth. The synthetic steroids mimic the natural cortisol by speeding up the development of organs – including the lungs – which means the preterm baby is much more likely to survive. However, they can lead to a phenomenon known as “accelerated aging.”
“Glucocorticoids are a clear lifesaver, but the problem with steroids is that they speed up the maturation of all organs. For the baby’s lungs this is beneficial, but for the heart and circulation system it can be damaging – it resembles accelerated aging,” the researcher from the Department of Physiology, Development and Neuroscience adds.
Why are steroids so harmful?
According to the team’s release, lab member Dr. Andrew Kane thinks this could result from steroids causing oxidative stress. Steroids lead to an imbalance of molecules known as free radicals, which result in a reduction in nitric oxide.
Nitric oxide is very beneficial to the cardiovascular system. It increases blood flow and has antioxidant and anti-inflammatory properties. A previous clinical study by researchers at the University of Oxford found those who had been exposed to glucocorticoid therapy as unborn babies, via their mothers, showed measures of cardiovascular health typical of people a decade older.
So, Prof. Giussani and the team combined the steroid treatment with statins, which are widely used to lower cholesterol and are known to increase nitric oxide. They gave the synthetic steroid, dexamethasone, combined with the statin, pravastatin, to rat pups.
Two other groups received dexamethasone or pravastatin alone, while a control group only received a saline solution. The team took measures of respiratory and cardiovascular function when the rats reached “childhood.” As expected, steroids produced adverse effects on heart and blood vessels. There were also molecular signs of cardiovascular problems.
If the rats received statins at the same time, however, the rats gained a measure of protection. Crucially, the statins did not affect any of the beneficial effects of steroids on the respiratory system.
The findings are published in the journal Hypertension.
South West News Servicer writer Mark Waghorn contributed to this report.