Brain challenge for premature babies

Babies born very prematurely have markedly less developed brains than those born at full term, a two-year Victorian study has revealed.

The study, which examined magnetic resonance images of premature babies’ brains and compared them with those of full-term infants, found that those born before 26 weeks gestation were at high risk of major brain development problems. This may explain why they are more prone to developmental difficulties later in life.

“Whatever happens in these babies’ brains, it’s not just injury, but abnormality,” said Terrie Inder, a pediatric neurologist at the Royal Children’s Hospital.

The study, headed by Dr Inder, involved three-dimensional brain scans of 260 babies born more than 10 weeks early and weighing less than 1250 grams. The team found the premature babies had about 30 per cent less grey matter – the brain’s thinking cells – than babies born at term. They also had about 40 per cent less white matter, which holds the brain’s fibre connections.

“What we found is that the brain does not grow as well when you’re born early,” Dr Inder said. The first group of children to be scanned under the MRI were now two, and were exhibiting some developmental delays compared with other children the same age.

It is hoped the findings will shed light on what happens to the brain when babies are born very early, and how that relates to the health and learning problems they are more prone to as they grow older. It will also help efforts to find ways to help nurture healthy brain development outside the womb.

Premature babies have a one in 10 risk of cerebral palsy; a quarter of them will need significant assistance at school; and they have a lower average IQ than term babies, Dr Inder said. More than 3000 babies are born in Australia at less than 30 weeks’ gestation. A full-term pregnancy runs to 40 weeks.

But the lifelong impact of extremely premature birth is still unknown, as it is only in the past decade that medicine has succeeded in keeping alive the tiniest babies – those born at 22 to 24 weeks.

The doubtful prognosis for some of these babies has sparked international debate and controversy.

In some parts of Holland babies born before 26 weeks are not resuscitated. (Experts in Australia argue the Dutch and Australian scenarios are not comparable, because premature babies born in Australia have a much better prognosis.)

Dr Inder, who is working on the study with colleagues from the Royal Women’s Hospital and the Howard Florey Institute, hoped that continuing research would reveal why the slowed brain development occurred, which would in turn help them to devise strategies to bridge the babies’ development gap.

Some of the team’s findings have been published in the Journal of Pediatrics, with several other papers under review.

Researchers were also focusing on the environment into which pre-term babies are born, Dr Inder said, including the levels of noise and light in neonatal intensive care units.

The conditions in which injury can be done to the infants’ brains, such as through infection or changes in blood pressure, was also being considered, even though it affected only a small proportion of the babies.

Dr Inder’s team is about to begin a trial looking at different ways of treating the babies to see if that helps their brain development, including having the mothers carry them on their chests, reducing medical tests, and making the unit as quiet and dark as possible to better replicate the womb.

Hormones were also suspected of playing a role in brain development, Dr Inder said. Her team was closely following a German trial in which premature baby girls – to date, researchers have been reluctant to recruit boys into the trial – are treated with oestrogen to see if this improves their brain development.

If that proved successful, exposure to oestrogen may become a future treatment option.

Lex Doyle, a consultant pediatrician at the Royal Women’s Hospital who is working on the study with Dr Inder, said although the differences in brain development uncovered so far were concerning “it’s still too early to know for sure what these MRI changes were showing”. There was no doubt that premature babies had a higher risk of long-term problems, Professor Doyle said, but “you’ve got to remember that most of them don’t have developmental problems; most of them are OK”.

Parents should contact their pediatrician if they are concerned about their child’s development.

Article from Fairfax Digital


Doctors launch National Premmie Day

Doctors are warning parents of a virus that is potentially life-threatening to infants, particularly premature babies, on the first National Premmie Day. The day has been launched with a warning about respiratory syncytial virus, or RSV, a common virus that causes about 6,000 children to be treated in hospital every year in Australia.

The risk of infection is at its highest from May to October. Associate Professor Dominic Fitzgerald from Sydney’s Westmead Children’s Hospital says premature infants are particularly vulnerable. “Premature babies are born with smaller lungs, if you like, with simpler architecture,” he said. “A legacy of that means that they don’t have the same reserve to fight infections.
“It’s true that lungs do repair and grow over time, but that takes several years so children, particularly in their first winter, are far more vulnerable if they’ve been born quite pre-term.”

Associate Professor Fitzgerald says the virus causes cold-like symptoms that can result in chronic breathing difficulties in infants. “It usually begins with nasal congestion just like the common cold,” he said. “Babies’ feeding declines because they need to breath through their nose, their nose gets blocked and so they can’t suck and feed well. “Often, the virus goes to the chest, giving them more difficulty with their breathing, so their hydration is compromised and their breathing compromised and in some cases necessitating a visit to hospital.”

Article from ABC News

National Premmie Day

Australia’s oldest premmie peer support groups have come together to launch Australia’s first national premmie day on June 12 this year to give these fragile infants a voice. More than 21,000 babies arrive early every year in Australia and more than 6,000 require critical life support and intensive around-the-clock medical intervention.

L’il Aussie Prems will be involved and will be holding an event in Wantira. For further information and event information please visit “events” under the menu.

www.lilaussieprems.com.au

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Celecoxib offers promise for premature babies

Scientists have found evidence that the cox-2 inhibitor celecoxib, a common pain reliever used to treat arthritis, may offer a new way to reduce the risk of the most common cause of brain damage in babies born prematurely.The work involves shoring up blood vessels in a part of the brain that in premature infants is extremely fragile and vulnerable to dangerous bleeding, which affects an estimated 12,000 children a year, leaving many permanently affected by cerebral palsy, mental retardation, and seizures.

“Stabilizing the blood vessels right before the baby is born is a tremendous opportunity to save the baby from potentially lifelong complications,” said Maiken Nedergaard, M.D., Ph.D., a neuroscientist at the University of Rochester Medical Center who is presenting the results at a neuroscience meeting, Brain ’07, in Osaka, Japan May 20-23.

The laboratory research was done primarily in a laboratory at New York Medical College led by neonatologist Praveen Ballabh, M.D. Ballabh’s team worked with Rochester neuroscientists including Nedergaard, Steven Goldman, M.D., Ph.D., and Nanhong Lou, Ph.D. A research article describing the work appeared in the April issue of Nature Medicine, which included a cover photograph taken by the Rochester team showing the brain cells involved in the brain damage seen in some premature infants.

The research is based on extensive brain studies of infants who died prematurely as well as on findings with newborn rabbits, whose brains resemble those of premature babies in some very important ways. The medication would need to be tested rigorously in pregnant women before being considered as a treatment for their babies. But the investigators point out that celecoxib is already used widely in people, including pregnant women, making a clinical trial in people feasible.

The researchers focused on a part of the brain known in developing infants as the germinal matrix, a temporary structure that is the birthplace of all brain cells in an infant. The structure runs like a jagged coastline just below spaces in the brain called ventricles, and in premature infants it’s extremely active, churning out new brain cells that migrate and settle into other parts of the brain.

“This is a very, very important part of the brain, from which neurons and glia cells migrate out to form all the layers of the brain,” said Ballabh, an associate professor in the Department of Pediatrics, Cell Biology, and Anatomy at New York Medical College, and a neonatologist at Westchester Medical Center.

The germinal matrix is designed to be active until around week 36 of gestation. Then, with most of the infrastructure of the brain in place, the germinal matrix disintegrates and shrinks into a much smaller brain region known as the ventricular zone in adults.

The problem is that the germinal matrix is as fragile as it is crucial during its brief existence. While it’s turning out new brain cells, it demands more oxygen and more blood flow, a demand that the body meets by building a network of temporary and very fragile, awkward, and leaky blood vessels.

In a normally developing fetus, the blood vessels do their job and then disappear by the time the baby is born. But when a baby is born prematurely, the structure is suddenly thrust into a role for which it is not designed, handling high rates of blood flow and pressure. It’s as if a building being outfitted with strong support structures is hit by an earthquake while the scaffolding is still up and construction is underway the whole structure is at risk of collapse.

In the case of prematurely born infants, the baby’s brain literally does not have the time to tie up its loose ends before blood vessels never intended to exist by the time an infant breathes on its own are suddenly required to carry blood. In the case of a bleed, the blood vessels break, cutting off the supply of oxygen to some brain tissue and directly damaging parts of the brain.

Babies most at risk are those born between 24 and 32 weeks gestation that weigh less than 1500 grams, or about 3 lbs., 5 ounces. About 20 percent of such infants have a bleed, known as a germinal matrix hemorrhage or an intraventricular hemorrhage. While the problem sometimes is very small and hardly noticeable, other times the bleed causes tremendous brain damage. The risk is greatest in the infant’s first 48 hours of life.

With funding from the National Institute of Neurological Disorders and Stroke and the Philip Morris Organization, the team set out to reduce the risk, focusing much of their effort on a molecule known as VEGF, which is largely responsible for answering the brain’s call for more oxygen by actively building new blood vessels. It’s the same compound that many cancerous tumors use to feed their demand for oxygen and to grow.

The goal was to make the germinal matrix a little hardier in cases of premature birth, by eliminating the active building of new, but very fragile, blood vessels that bleed more easily than established blood vessels. The team used celecoxib to knock down the production of cox-2, which in turn slowed production of VEGF. The team also studied an anti-cancer drug known as ZD6474, which affects another molecule, angiopoietin-2, that the body uses to build blood vessels.

The team found that in human brain tissue, the compounds greatly reduced the production of cells used to build blood vessels, and decreased levels of angiopoietin-2 and VEGF, the two molecules very active in building new blood vessels.

Results were dramatic in female rabbits that were given the drugs for two days before delivering their offspring prematurely. The team showed that celecoxib cut the risk in offspring of having a moderate or severe bleed in half, from 90 percent to 45 percent. The percentage was reduced even more when ZD6474 was used as well, from 45 to 27 percent, but Nedergaard and Ballabh point out that ZD6474 is a very potent medication not likely to be given to pregnant women in the near future.

Overall, the best way to prevent the problem, doctors say, is to do everything possible to allow a pregnant woman to carry a pregnancy for a full 40 weeks. So doctors put a great deal of effort into preventing preterm labor. But when premature labor can’t be prevented, doctors do have a few tools at their disposal to try and prevent bleeds in the germinal matrix.

Steroids, commonly used to help develop the lungs of a premature infant, can help prevent bleeds too. And recent research has shown that indomethacin, which like celecoxib is a non-steroidal anti-inflammatory drug, has been shown to help prevent such bleeds and is used to treat premature infants for other problems, but it has some severe side effects, Ballabh said. And a 2002 report by researchers at Washington University and Northwestern University indicated that celecoxib the same drug that Nedergaard and Ballabh showed helps prevent the bleeds might also be effective in preventing preterm labor.

“This work is very exciting, but the work is ongoing, and we must investigate the use of celecoxib more thoroughly before considering it for widespread use to prevent this problem,” said Ballabh. “We can fix many problems in the premature infant, but brain damage is one problem that cannot be fixed it must be prevented. Right now there is nothing available that has been shown to be really effective at preventing this problem.”

Article from News-Medical.net 

Kangaroo Cuddles Help Premature Babies

Georgia was born 10 weeks premature. Now, at 32 weeks, she is placed skin-to-skin on her adoring mother’s chest, tucked into place under mum’s jumper.

“Kangaroo care”, as it is officially known, involves parents cuddling up to premature infants each day for up to two to three hours, even if the baby is still attached to an oxygen tube. The babies, placed on their parent’s chest, are kept warm by the adult’s body heat.

But is such intimate contact good for premature children, or should they be left to grow in peace in their incubators? A study by three Israeli universities has concluded that the skin-to-skin contact between premature infants and their parents benefits both.

According to the study, infants receiving the care were more socially alert and their developmental scores were higher at six months than those left in incubators while in hospital.

“Mothers who provided kangaroo care were less depressed, perceived their infants as less abnormal and provided increased maternal affiliative behaviors during the hospitalisation,” the report said.

“Parents from the kangaroo care group provided a more sensitive and appropriately stimulating home environment and . . . mothers were more sensitive, adaptive, warm and resourceful during social interactions at six months.”

The study involved 73 pre-term infants who received the close-up care and 73 who did not. The report said the study was one of the first to look at the impact of close-up care for the first six months of life.

The Royal Women’s Hospital, where Georgia is staying, had encouraged kangaroo care for about 10 years, said intensive and special care nursery head nurse Marie Campbell.

“The positives outweigh the negatives,” she said. “We used to be worried about babies getting cold … we used to be more worried about handling the babies.”

Ms Campbell said that not only did kangaroo care calm babies, it also helped their mothers express more breast milk.

Georgia’s mother, who asked not to be named, said she loved being so close to her daughter.

“We’ve been waiting to do a kangaroo cuddle for a few weeks,” she said. “It brings you as close to the baby as you can get.”

Article from the Age