Protecting babies from dangerous free radicals

Dr Suzanne Miller leads a group of researchers at the Monash Institute of Medical Research's Ritchie Centre who are looking at how the foetus develops, particularly the brain, and how to protect it. She very concerned about free radicals, not the activist kind, but the kind overproduced in the womb when poor oxygen supply or infection can lead to brain and other damage. But her team has identified a way to deal with them.

Dr Suzanne Miller is a foetal physiologist. She investigates how foetuses grow and what happens when things go wrong. That could be asphyxia, an acute lack of oxygen just before or at birth, chronic hypoxia, a moderate but ongoing lack of oxygen during pregnancy, or infection, which causes inflammation of the membranes that surrounds a foetus.

Such events during pregnancy or at birth can lead to poorly developed organs, including the lungs, heart and brain. Suzanne is most concerned with the brain because its abnormal development can lead to learning disabilities or cerebral palsy - the most common physical disability in children, which leaves them with little, if any, movement in their arm or legs.

These possibilities keep everyone at the Ritchie Centre - research scientists like Suzanne and the clinicians with whom she works - focused on finding new ways to minimise and repair damage to unborn and newborn babies.

Her teams' latest treatment for asphyxia and chronic hypoxia, which they've tested successfully on animals, uses an antioxidant known as melatonin to protect foetuses and newborn babies against oxygen free radicals.

andldquo;A placenta that's not functioning properly during pregnancy can result in the production of oxygen free radicals, which can also be produced in healthy pregnancies at the time of a difficult birth,andrdquo; she says. andldquo;It's these free radicals that are thought to do most much of the damage to vulnerable brains.andrdquo;

Melatonin is a natural hormone that sets our circadian rhythms, but Suzanne and her team found that its powerful antioxidant properties reduced oxygen free radicals, especially the highly destructive hydroxyl radical.

The potential treatment offers hope to the eight per cent of pregnant mothers with malfunctioning placentas that can deprive their babies of oxygen and cause intrauterine growth restriction or IUGR.

'By giving melatonin to the mum, we're not completely ameliorating the production of oxygen free radicals in the placenta, but we're certainly holding it at a more appropriate level, which is below the level normally found in IUGR pregnancies,' Suzanne says.

Babies suffering from IUGR, which ultrasound can detect at about 20 weeks, risk being stillborn or suffering heart and lung damage, not just brain injury.

Another of her team's potential treatments for high-risk pregnancies uses an anti-inflammatory compound to treat chorioamnionitis, an infection of the foetal membranes that often leads to preterm births and high rates of cerebral palsy.

After discovering that melatonin didn't help here, Suzanne and her team turned to Sulfasalazine, a broad-spectrum anti-inflammatory drug, used to treat pregnant women with painful arthritis. Having found that it also reduces inflamed foetal membranes, they plan to design a more targeted drug.

While treatments to prevent damage are at the forefront of their work, Suzanne and her Ritchie Centre colleagues know that preventing brain injury is not always possible. They're now trialling the use of stem cells, taken from placentas after birth, to repair damage to babies in the womb or at birth.

Their research is at an early stage, but the results from animal testing are promising. When they injected human amnion epithelial cells into foetal lambs, they weren't sure they would gain access to the brain, which Suzanne says 'is very fussy about what can and can't pass through its strictly controlled blood-brain barrier'.

'But we've found them in quite large numbers within the brain, which suggests that they're homing to the sites of injury. Whether or not they're repairing injury at this stage, we're not sure, but, fingers crossed. They're certainly getting there.'

Suzanne credits the Ritchie Centre's success at finding novel treatments for at-risk mothers and babies to the constant collaboration and interaction between the scientists and practising doctors who work there.

'When we're doing experiments, we have all hands on deck. We have people saying, 'We should try this,' or 'What about doing this kind of targeted therapy.' This collaborative approach to research really works.'