A NEW drug that prevents breathing problems common in premature babies may result in fewer infants being put on ventilators during the first weeks of life, and fewer deaths among the newborn.

The drug, thyroid-releasing hormone (TRH), is given to mothers at risk of giving birth prematurely. Administered days or even hours before labour, it crosses the placenta and, by stimulating hormone production, artificially matures the lungs of an immature foetus. The baby is thus less likely to need extra oxygen when it is born or to develop chronic, sometimes fatal, lung disease.

Until recently, all doctors could do for premature babies with respiratory problems was keep them on a ventilator until their lungs matured sufficiently. Now a new approach is being developed to speed up the maturing of the lungs in the womb, enabling the premature baby to start breathing the moment it is born.

At birth, the lungs must perform a remarkable feat. After almost nine months of secreting fluid, they have to start absorbing it instead, so that the baby can take its first lungfuls of air.

Doctors are trying to identify how this all-important fluid-absorbing mechanism works - and why it sometimes fails. Professor Richard Olver of Ninewells Hospital and Medical School, Dundee, is carrying out research for the Wellcome Trust and British Lung Foundation. 'We are finding out how babies' lungs switch from liquid to air,' he says. 'This will lead to a better understanding of how we can help babies with breathing problems.'

Intriguingly, Professor Olver's research has shown that the way a newborn baby starts to breathe is similar to what happens in a salmon when it moves from the fresh water river to the open sea and has to start pumping salt out through its gills. In the baby, too, a pumping mechanism starts to expel the salty water that fills the lungs, sending the fluid in the opposite direction.

During its time in the womb, hormones from the unborn baby's thyroid and adrenal glands mature the cells lining the lungs, preparing them for the switch from pumping fluid into the lungs to pumping it out.

At birth, another vital hormone, adrenalin, comes into play. In a normal vaginal labour, the stress of passing through the birth canal raises a baby's adrenalin to astonishing levels, much higher than a woman in labour or someone having a heart attack. This surge of the 'fight or flight' hormone triggers the cells lining the lungs into absorbing the fluid instantly, so that the baby can start breathing normally at birth.

Sometimes the system fails to work, depending both on the type of delivery and the baby's maturity.

Babies delivered by Caesarean section before labour starts have low levels of adrenalin. Their lungs eventually start absorbing fluid, but this explains why Caesarean babies are often born with fluid welling from their mouth and nose and it can take between several hours and a couple of days for them to start breathing properly. The baby may need to be kept in the special care unit and be given extra oxygen. This is distressing, but rarely fatal.

For babies born prematurely - before 37 weeks' gestation - the consequences can be more serious. Even if they are born vaginally, and thus experience the adrenalin surge, their lung lining is too immature to respond in the right way. They fail to make the rapid transition from secreting fluid to absorbing it and, as a result, often have waterlogged lungs and suffer from breathing difficulties.

In addition, premature babies' immature lungs have not started producing enough surfactant, the chemical that holds open the airsacs. Without surfactant, the airsacs collapse at the end of each breath, causing respiratory distress syndrome - the single most important cause of death in newborn babies. A combination of surfactant deficiency and immature lungs that continue to secrete fluid, even when the baby is on a ventilator, can damage the lungs and lead to chronic lung disease. Some children spend months in hospital and need extra oxygen for up to two years.

For some years now it has been known that giving adrenal steroids to women at risk of premature delivery can help to mature the baby's lungs before birth, increasing surfactant production and cutting the risk of respiratory distress syndrome. Given, preferably, 24 hours or more before labour, these synthetic hormones work quickly to advance the development of the lungs by about two weeks.

Yet despite their effectiveness, some doctors still have doubts about using them, and only a minority of babies who could benefit are actually given steroids before birth.

Premature babies can also be given surfactant drugs after birth. These are effective but much more expensive than steroids. 'The appropriate use of surfactant could potentially reduce deaths from respiratory distress syndrome by up to 40 per cent, or 1,400 babies, a year,' Richard Cooke, president of the British Association of Perinatal Medicine, says.

But even with steroids and surfactant therapy, many babies still contract lung disease. The newest research indicates premature babies could also benefit from thyroid-

releasing hormone, in addition to the steroids. TRH stimulates the foetal thyroid gland, which makes the baby increase its production of thyroid hormone. This, in turn, helps to mature the fluid-absorbing system in the lungs.

Doctors say it is too early to estimate by precisely how many weeks TRH can develop immature lungs. But Professor Cooke says: 'The trials that have been carried out so far in the United States indicate that, compared with steroids on their own, giving TRH as well reduces chronic lung disease by the same amount again.

'This is an exciting area of research, because it shows that with drugs such as steroids and TRH you can artificially mature the immature foetus so that it can cope with normal life.'

A random study of 1,200 women to assess the effectiveness of giving TRH along with steroids is under way in Australia, co-ordinated from the Queen Victoria Hospital, University of Adelaide. The results should be available within a year.

Here, Dr Luca Fusi at Hammersmith Hospital is setting up a trial on TRH involving 180 mothers-to-be, and the Perinatal Trials Service, at the Radcliffe Infirmary in Oxford, also plans to start a multicentre trial soon. 'The time is right for a large study,' Adrian Grant, director of the Perinatal Trials Service, says. 'There is promising evidence TRH may be useful; now we need to show it is both safe in the long term, and beneficial in ways that matter to parents.'

An alternative approach is to give the baby the actual thyroid hormone (T3) immediately after birth, while the adrenalin level is still high. Dr Dafydd Walters, reader in paediatrics at University College Hospital, London, says: 'We have already given T3, along with hydrocortisone, to six small babies, who were at death's door. It works very fast. None of them died and none had chronic lung disease, and we have now established what dose to give. Each new advance in this area helps a baby's chances of getting away without lung disease.'

(Photograph omitted)

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