New techniques mean tailored treatments for premature babies, writes Denise Cullen

ANDREA Krieger’s son Angus faced tough odds when he was was born 15 weeks early five years ago. Sophisticated medical interventions over the past two decades have dramatically increased survival rates for very premature babies.
Health

But the flipside of these advances is that babies born pre-term, particularly if, like, Angus they are born before 26 weeks’ gestation, are likely to be dogged by a host of neurodevelopmental difficulties, many of which persist into adult life.

“When Angus was born at 25 weeks, he was given less than a 50 per cent chance of survival,” Krieger recalls. “We were told that the babies like him that do survive will have brain injury, or delayed development, along with other health issues.

“It was a very difficult time, but for me, having all the cards laid out on the table, and knowing all the possibilities was important, because with knowledge, there’s power, and your choices can be more informed.”

While the balance of the risk of health problems had been thought to be still on the baby’s side in the case of a pre-term birth, in population terms the dangers are relatively high. One study, published in the journal Brain (2007;130:667-677), revealed that 10-15 per cent of very pre-term infants developed cerebral palsy, while up to half had other significant problems such as lowered IQ, attention deficit hyperactivity disorder (ADHD), anxiety disorders and learning disabilities.

To make matters worse, trying to predict which pre-term babies will experience these outcomes using standard clinical indicators — gestational age, birth weight, and complications during the neonatal period — has proven problematic. Some children considered to be at high risk for developmental dysfunction seem to do just fine; others who are predicted to do well do not.

But a novel study in Melbourne is using high-tech magnetic resonance imaging (MRI) to uncover vital clues as to how premature babies will develop, by identifying specific abnormalities in their brains.

Doctor Peter Anderson, a psychologist and senior research fellow at the University of Melbourne and Murdoch Childrens Research Institute (MCRI), says the long-term study will follow 230 children recruited as premature babies from 2001-2003, throughout childhood and hopefully into adulthood.

In doing so, it will focus on the consequences of brain abnormalities revealed in the neonatal period on subsequent brain development and neurobehavioural outcome in this high-risk population.

“Cranial ultrasound is the standard technique for assessing brain injury in premature infants, and while this technique is good at picking up significant abnormalities, it is not as sensitive when it comes to picking up more common and subtle brain abnormalities,” Anderson says.

“We have also demonstrated that brain MRI scans are more predictive of early developmental delay than cranial ultrasound.”

Krieger’s son was recruited into the MCRI study and underwent an MRI scan on his due date.

“It showed that his brain was immature in general, but that was always going to be the case because he was a premature baby,” his mother says.

“The researchers then linked the information in the scan to the types of physical, motor and intellectual problems Angus may be at risk for, and the challenges he could face in the future.”

As a result of that information, the family engaged in early intervention services including speech therapy, physiotherapy and occupational therapy through Victoria’s Broad Insight Group.

“He reached all his milestones, like learning to crawl — he just reached them later,” Krieger said.

Anderson points out that MRI studies, such as the one conducted in Melbourne, have revealed a far higher incidence of brain abnormalities in premature babies than was believed to exist, with about 70 per cent later having pathology ranging from mild to severe.

For fraught parents already struggling to deal with the health and other issues that typically confront their premature infants, such figures sound anything but comforting.

Yet through delving into the reasons why particular patterns of difficulty occur, researchers hope to devise intervention and remediation strategies to bridge the babies’ developmental gaps.

“Our ability to identify children at risk for different types of developmental delay is critical for selecting the most appropriate early intervention program for each child,” says Anderson.

While no one can explain exactly why early intervention works, most people agree it does. It’s generally believed young, malleable brains can be “rewired”, at least to some degree, through speech therapy, occupational therapy, physiotherapy and other interventions.

MRI scans have shown that babies born prematurely not only tend to have smaller brains overall, but that certain parts of the brain — in particular the white matter, the cabling that facilitates communication within the brain — are at risk of injury.

“Research tends to suggest that prematurity has a selective effect on specific regions of the brain, or that there are regions of specific vulnerability,” says Anderson.

One of these regions is the corpus callosum, which links the right and left hemispheres of the brain, and plays an important role in establishing which sides of the brain become specialised for performing particular tasks.

According to a previous paper in Brain (2004;127:2080-2089), research conducted on adolescents aged 14-15 years revealed that thinning of the corpus callosum was often observed in those born very pre-term.

This was strongly correlated with their deficits in verbal intelligence and verbal fluency, and is believed to be the case because the corpus callosum is integral to high-order cognitive processes, such as language, which require complicated information transfer between both hemispheres of the brain.

The cerebellum, located at the base of the brain and playing a crucial role in motor co-ordination, muscle tone and different types of cognitive functioning, including planning ability, also seems susceptible to the effects of early birth.

The hippocampus is further implicated in the learning difficulties, particularly memory impairments, that children born prematurely may demonstrate upon reaching school age.

Yet the reasons why prematurity causes these changes in the brain remains something of a mystery.

What is known is that during the third trimester, the brain is maturing at a rapid rate and the developmental events that are occurring during this period are likely to explain why some parts are more vulnerable than others to alteration by pre-term birth.

Fever, infections, breathing difficulties and hypoxic episodes (during which the babies’ brains receive insufficient oxygen) are also suspected to play a part.

Even the medical interventions designed to save their lives and the environment of the neonatal intensive care unit — typically involving bright lights, loud noises and painful medical procedures — might expose fragile bodies and brains to damaging stimuli.

“Their sensory systems are immature and just aren’t ready for all of that input,” Anderson says. “What impact it all has on the brain is not known but it is likely to be negative.”

“But there’s no simple or single thing that’s causing these abnormalities in pre-term babies’ brains … It’s clear that there are a number of factors that are involved, and many of these are inter-related.”

While MRI has been in use for many years, it is still not used routinely with very premature infants, despite the high rates of brain abnormalities and neurodevelopmental problems. This is partly because it is difficult to scan very sick infants.

“Before Angus went for a repeat scan at two years old, we recorded all the screeches and grinds and other awful sounds from the machine and played that to him at bed-time, so he was more comfortable,” says Krieger.

But she says it was worth all the trouble: “There was huge development in his brain right up to the skull… he’s perhaps still behind his peers, but I could see the difference.”

Now aged 5, and looking forward to kindergarten, Angus’ life is not without its challenges. His muscle tone remains low — which means, for instance, that producing the sounds required for speech is difficult for him, and as a result he continues to have speech therapy and physiotherapy. But as children like Angus start to be scheduled for the scans due when they turn seven, and the associated neuropsychological assessments, Anderson is hopeful of gaining insight into some of the factors that facilitate brain development in this vulnerable group of children.

“The group that we’re following up is the largest group of children anywhere in the world to undergo neonatal scans and follow-up,” says Anderson. “While most infants with severe brain injury develop marked disabilities, others have reasonable outcomes, (and so) identifying the processes associated with such recovery is of major importance.”

Article & photo from The Australian

Folic acid supplements taken for a year before pregnancy can cut the risk of premature births by 70% and save thousands of lives, researchers have found.

One in three babies born under 28 weeks die, and many others face lifelong disability. Experts say the research, based on a study of nearly 40,000 women, adds weight to calls for flour and bread to be fortified with folic acid.

Doctors have long recommended that women planning a family take folic acid supplements to reduce the risk of neural tube defects, including spina bifida, which can cause profound disabilities. But the latest study shows it has other benefits.

The Royal College of Obstetricians and Gynaecologists described the study as “extremely exciting”. Tim Draycott, a consultant obstetrician and gynaecologist, said: “[Premature births] are a tremendous burden on the children, the families and society … Anything that is potentially beneficial and particularly something as safe as folic acid – we would welcome as an intervention.”

Reducing the number of premature births would also ease the burden on the NHS. Cots in premature baby units cost between £43,672 and £256,248 a year, according to the National Audit Office, depending on the level of care they provide.

More than 60,000 babies are admitted to such units each year and the total cost to the NHS in England is £420m.

In the US, it has been compulsory for manufacturers to enrich cereal-based products with 140 micrograms of folic acid per 100 grams since 1998.

The RCOG recommends that flour should be boosted with 240mcg of folic acid per 100g grams to prevent brain and spinal cord defects. Draycott said fortifying foods was more likely to be successful than asking all women of child-bearing age to take the vitamin as a supplement. According to the college only about a third of women take folic acid supplements before becoming pregnant.

The latest study looked at the effect of taking folic acid – the synthetic form of vitamin B9 – before conception. The team used information from a National Institutes of Health study about the pregnancies of 38,033 women.

By comparing groups of women who had taken folic acid for different lengths of time, the researchers found the supplement could cut the risk of premature delivery by 70% for very early premature births – 20 to 28 weeks of pregnancy – and by 50% in births after 28 to 32 weeks.

The study will be presented at the annual meeting of the US Society for Maternal-Fetal Medicine today.

In 2005-06, the latest year for which figures are available, 4,150 babies were born between 20 and 28 weeks of pregnancy. Babies born this early run a high risk of developing disabling conditions such as cerebral palsy, learning difficulties, blindness and chronic lung disease.

According to Radek Bukowski, an assistant professor of obstetrics and gynaecology at the University of Texas, who led the research, the study was prompted by previous research which showed that women who gave birth early had lower levels of folic acid in their blood.

Professor Gordon Smith, an expert in obstetrics and gynaecology at Cambridge University, said: “What you can now say is that folic acid has more general effects in pregnancy, which bolsters the case for fortifying flour. A lot of pregnancies aren’t planned, so most women don’t take folic acid supplements because they won’t be thinking about pregnancy.”

Until the research is confirmed though, Draycott said the findings should be treated with caution. Large epidemiological studies of this kind are prone to throwing up spurious results if the true factor causing health benefits is linked to whether women take folic acid or not. “The difficulty is that folic acid could be a marker of other good behaviours,” he said, for example the people who take folic acid might also be well off and attend antenatal classes.

In May last year the Food Standards Agency said ministers should order the mandatory fortification of food with folic acid. But the FSA has not decided whether to add the vitamin to bread or flour because of concerns that people from ethnic minorities do not eat processed bread. There is also some evidence that folic acid has adverse effects on older people with a deficiency in vitamin B12.

“This is another piece of positive research showing fortifying is a good thing,” the FSA said.

Bliss, the premature baby charity, said: “This … could signal a positive new approach for reducing the number of premature births.

“We look forward to seeing further work done in this area – anything that improves outcomes for babies and increases their chance of having the best start to life is a very welcome development.”

Article from The Guardian