How statins might help premature babies

By Mark Waghorn via SWNS

Statins could hold the key to saving the lives of premature babies, according to new research.

The cholesterol-lowering drugs also reduce the risk of cardiovascular problems in newborns, say scientists.

Experiments in rats suggest they should be administered in combination with steroids - the gold standard treatment.

Medications called glucocoticoids are commonly given to infants delivered before 37 weeks of gestation.

But they have potentially fatal side effects on their heart. Statins reduce the risk, said
lead author Professor Dino Giussani.

He explained: "Our discovery suggests combined glucocorticoid and statin therapy may be safer than glucocorticoids alone for the treatment of preterm babies.

"We're not saying to stop using glucocorticoids, as they are clearly a life-saving treatment.

"We're saying to improve this therapy - to fine tune it - we could combine it with statins.

"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 University team plan to replicate the test in sheep, which have similar physiology to humans, before conducting human clinical trials.

About 1 in 10 babies (10.5% of live births) are born preterm in the United States.

Rising rates of obesity and type 2 diabetes are behind the rise.

Globally, one in ten infants are premature - rising to 40 percent in low-income countries.

It raises the risk of the newborn dying or being left with health issues that may persist and develop over the life course.

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, the newborn lungs would be too stiff, which leads to respiratory distress syndrome (RDS) and could be fatal.

Glucocorticoid therapy is the established treatment - given via the mother before the baby is born or directly to the baby after birth.

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.

But they can lead to a phenomenon known as 'accelerated aging.'

Prof Giussani said: "Glucocorticoids are a clear lifesaver, but the problem with steroids is 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."

Lab member Dr. Andrew Kane thought 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 anti-oxidant and anti-inflammatory properties.

A previous clinical study at Oxford University 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 colleagues 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 third, which acted as a control, got a saline solution.

Measures of respiratory and cardiovascular function were then taken when the rats had grown to 'childhood.'

As expected, steroids produced adverse effects on the heart and blood vessels. There were also molecular signs of cardiovascular problems.

But if statins were given at the same time, the rats were protected. Crucially, the statins did not affect any of the beneficial effects of steroids on the respiratory system.

The findings are reported in the journal Hypertension.