Combining life-saving steroids with statins for preterm babies cuts risk of long-term cardiovascular disease, University of Cambridge study suggests

The risk of long-term cardiovascular problems caused by giving life-saving steroids to babies born prematurely can be reduced by combining them with statins, a Cambridge study suggests.

In high income countries one in 10 babies is born preterm - before 37 weeks - and this proportion can increase to almost 40 per cent in low- and middle-income countries.

Preterm birth is one of the biggest killers in perinatal medicine, as babies born this early miss out on a crucial final developmental stage in which the hormone cortisol is produced and released exponentially into their blood. This is vital in helping their organs and system to mature.

Cortisol ensures lungs become more elastic, meaning they can expand so the baby can take its first breath. Without it, new-born lungs are too stiff, which can lead to respiratory distress syndrome (RDS) and can be fatal.

The standard clinical approach for preterm babies is glucocorticoid therapy, given via the mother before birth and/or directly to the baby afterwards.

The synthetic steroids mimic the natural cortisol by speeding up the development of organs such as the lungs, meaning a preterm baby is much more likely to survive.

Professor Dino Giussani from the Department of Physiology, Development and Neuroscience at the University of Cambridge, lead author of a paper published in Hypertension, said: “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 ageing.”

An earlier clinical study by Professor Paul Leeson’s laboratory at Oxford University found that people exposed to glucocorticoid therapy as unborn babies, via their mothers, showed measures of cardiovascular health typical of people a decade older.

Cambridge researcher Dr Andrew Kane, who was involved in the new study, which used rats, thought this accelerated ageing could result from steroids causing oxidative stress.

Steroids lead to an imbalance of free radicals, leading to a reduction in nitric oxide.

The cardiovascular system required nitric oxide as it increases blood flow and has anti-oxidant and anti-inflammatory properties.

Statins are widely used to lower cholesterol and are known to increase nitric oxide, so researchers gave the synthetic steroid dexamethasone combined with the statin pravastatin to rat pups.

Other groups received dexamethasone alone, or pravastatin alone, while a control group received saline.

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

The steroids produced adverse effects on heart and blood vessels and molecular indices associated with cardiovascular problems.

If statins were given at the same time, however, the rats were protected from these effects. The statins did not affect any of the beneficial effects of steroids on the respiratory system.

Prof Giussani said: “Our discovery suggests that 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 that 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.”

The team now aim to replicate the experiment in sheep, which have a similar physiology to humans, before conducting human clinical trials.

The research was funded by the British Heart Foundation and the Biotechnology and Biological Sciences Research Council (BBSRC). Dr Andrew Kane was supported by the Frank Edward Elmore Fund and the James Baird Fund.