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Healing the Youngest Brains

UCLA Health
Shari Roan

Jade Loop had the perfect pregnancy. So when she went into labor on September 26, 2012, Loop and her husband, Tomer DeVito, didn’t anticipate that the birth of their first child would be anything less than perfect as well.

That’s not how it turned out.

Sage DeVito was born, after many hours of labor, on September 28 at UCLA Medical Center, Santa Monica. But instead of letting out a wail as he gulped in his first breaths of air, the baby was silent, limp and blue.“The medical team started to work on him immediately,” Loop recalls. “He wasn’t breathing. He did not cry. They rushed him out of the room. It was very scary. I didn’t even get to see him.”

A short time later, doctors told the couple that Sage experienced a lack of oxygen at birth and may, as a result, have sustained a brain injury. But, one of the doctors added, “The good news is that you’re here.”

UCLA has one of the foremost neonatal-intensive-care programs in the country and the skill and advanced technology to address such serious issues as oxygen-deprivation during birth. In Sage’s case, the treatment was therapeutic hypothermia, a protocol that is among several advances in neonatal care aimed at improving the outcomes for full-term and premature babies born with brain injuries.

Sage was rushed from Santa Monica to the neonatal intensive-care unit (NICU) at Mattel Children’s Hospital UCLA, where he was placed on a special blanket, through which cold water is circulated, to gradually and carefully lower his core temperature to about 92.3 degrees F. (Another method utilizing a cooling cap can also be used instead of a blanket.) By cooling the body, metabolic processes slow down, conserving energy needed for healing and calming inflammation resulting from the initial injury. The goal is to spare the infant from some degree of disability or developmental delay that might otherwise accompany such an injury.

“In the last decade, we’ve come to understand that, with brain injuries that are moderate, we can make a difference,” says Sherin U. Devaskar, MD, Mattel Executive Endowed Chair of the Department of Pediatrics and physician-in-chief of Mattel Children’s Hospital UCLA.

After three days in the NICU undergoing hypothermia treatment, Sage was warmed to a normal temperature and underwent an MRI exam, which showed no brain damage. Today, he is developing normally and hitting all of his developmental milestones.

“The people caring for him were the most amazing people I’ve ever been with,” Loop recalls. “I felt very lucky to be there.”

Knowledge about brain injuries in infants has exploded in the past decade. Many of these injuries are, as in Sage’s case, the result of hypoxic ischemic encephalopathy (HIE) – which means the baby is deprived of an ade-quate supply of oxygen. The condition affects one to two babies per every 1,000 births in the United States and results in a mortality rate of about 15 percent. About 20-to-25 percent of surviving babies are permanently disabled with neurodevelopmental impairment.

Another major source of infant brain injuries is prematurity, which occurs in one-of-every-nine births in the United States. In about 10 percent of cases, premature babies develop cerebral palsy, while as many as half have some type of cognitive disorders or learning disability. Still other types of infant brain injuries occur because of problems in the pregnancy, such as intrauterine growth restriction.

Whatever the cause, infant brain injuries are shocking to families who are expecting to embark on one of the happiest times of their lives, Dr. Devaskar notes.

“A couple plans for a child. They go through nine months of pregnancy with nothing wrong. They do everything right,” she says. “I’ve had parents tell me: ‘We were healthy. We ate right. We took vitamins.’ And yet, at the last minute, something goes wrong, and they have a child who is disabled for the rest of his or her life. That is devastating.”

Neonatologists are trying to mitigate that devastation with such treatments as therapeutic hypothermia. The treatment is considered among the most exciting recent developments in neonatal medicine, says Meena Garg, MD, clinical professor of pediatrics and neonatology at the David Geffen School of Medicine at UCLA.

“Sometimes the blood supply from the mother to the fetus is interrupted, such as from placenta abruption or cord prolapse,” she explains. “When the blood supply is cut off, there is an immediate injury to some of the brain cells and neurons.”

More important, after this initial insult to the brain, another destructive and more insidious process continues to occur over the next three-to-seven days. The initial injury deprives the brain cells of the energy – in the form of oxygen and glucose – that is essential for brain function. This injury triggers inflammation that can result in secondary brain damage for several days after the initial injury. Therapeutic hypothermia helps blunt this secondary damage. As the body and brain are cooled, less energy is needed for brain function, minimizing injury. Cooling also interrupts the process of inflammation that causes the death of brain cells and neurons.

“The hypothermia slows down the ongoing damage in the brain,” Dr. Garg says. “It affects all aspects of inflammation in the brain.”

The key to successful treatment, says Dr. Garg, is applying the therapy within six hours of birth. In some cases, UCLA air-transport teams have flown as far as California’s Central Valley to pick up and return newborns to UCLA for timely treatment.

“Of all the transport types I do, transporting babies with hypoxic brain injury can be the most challenging, mainly because of the time factor,” says neonatologist Caroline Gibson, MD, a member of the air-transport team. “Sometimes we’re running through the hospital with the isolette. The protocol gets activated before I go out to pick up the baby, so as soon as we arrive, the whole team is waiting at the bedside.”

So far, UCLA has used therapeutic hypothermia to treat about 80 infants, and the outcomes have been good. International studies show babies who receive therapeutic hypothermia have a 20-to-25 percent improvement in outcomes compared to babies who receive standard care.

“In the United States, the incidence of HIE has not changed over the years,” Dr. Garg says. But, she adds, babies used to get only supportive care – nutrition, oxygen and ventilation. “There was no specific treatment for the brain injury up until now. Therapeutic hypothermia is the first thing we’ve had to help these babies by preventing ongoing brain damage. Parents are relieved that there is something to help their baby; they want us to do everything we can.”

And further advances may be on the way. Childhood brain and behavior compose one of four core areas targeted by the new UCLA Children’s Discovery and Innovation Institute, which was founded to promote innovative and groundbreaking collaborative research to improve the lives of children.

Other advances in neonatal care, such as continuous electroencephalography (EEG) monitoring, have augmented the care of brain-injured newborns, Dr. Garg says. EEG measures and records the brain’s electrical activity. The technology is important in the care of brain-injured newborns in order to diagnose seizures, which also can damage the brain. About 60-to-70 percent of brain-injured newborns have seizures. But, unlike standard EEG, continuous EEG allows for constant surveillance of the baby. Data from contin-uous EEG monitoring can be sent, via wireless connection, to neurologists’ offices or homes for frequent and rapid assessment.

The neonatal team at UCLA also is using MR imaging to assess damage to the brain. “If you see major changes on MRI, you caution the family that this child needs close follow-up,” Dr. Devaskar explains. “Before we had this imaging, we could only rely on the clinical exam alone.”

In addition, UCLA researchers are studying whether or not seizure medications will improve the outcomes for babies who have had therapeutic hypothermia. They are looking for biomarkers in the blood – chemicals that are clues to what’s happening in the brain – that can predict a baby’s eventual outcome, Dr. Devaskar says.

Moreover, studies are underway on whether or not stem cells can be used to repair the developing brain. Laboratory studies show that stem cells can be coaxed to become brain cells in a dish. Now scientists are studying how they can get those stem cells to the parts of the brain where they’re needed. These studies are at the pre-clinical stage of development.

Other therapies are aimed at babies with brain injuries that are caused by insults other than from lack of oxygen. Hypothermia, for example, doesn’t help preemies, who are especially prone to brain damage. Premature babies are benefiting from the enhanced imaging techniques, such as continuous EEG and MRI, because the information provides doctors and parents with a roadmap for the future.

“With better imaging, we’re able to prognosticate,” Dr. Devaskar says.

“We then get these babies into an early intervention and follow-up program very quickly. They get vision, hearing, IQ and fine-motor testing.”

Dr. Devaskar points out that it really does take a village – neonatologists, pediatric neurologists, neuroradiologists, the neonatal/pediatric transport team and the entire staff of the NICUs – to ensure optimal and timely care of these babies.

“With early intervention programs, we’re making a difference,” she says.

Indeed, they have made a world of difference for Jade Loop and her son.

Each new skill that Sage develops, such as sitting up and holding a cup, is a cause for celebration. “All of the other little things about being a new mother don’t matter to me – not getting enough sleep or the baby crying,” Loop says. “It doesn’t matter. This is a miracle.”

Concussion Discussion 

Many brain injuries to older children and teens occur during participation in sports, more than 1 million each year in the United States, according to the American Academy of Neurology (AAN). But until recently, these injuries often went unrecognized – and untreated.

“Mild concussive injuries that were overlooked in the past are now coming to attention,” says Christopher Giza, MD, associate professor of pediatric neurology and neurosurgery. “When I was a kid, mild injuries to the brain weren’t really recognized. Nobody took you out of the game. You would continue participating in that activity, and you could get injury on top of injury.”

Dr. Giza is the co-author of newly released guidelines from the AAN on evaluating and managing athletes with concussion. Among the recommendations: An athlete with suspected concussion should be removed from play and not return until he or she has been assessed by a health professional trained in concussion. Athletes should return to play slowly and only after all acute symptoms are gone.

But more research is needed on traumatic brain injuries in youths, Dr. Giza maintains. There is some evidence, for example, that younger brains may be more vulnerable to traumatic brain injury than adult brains. Compared to collegiate athletes, high school athletes seem to have a longer duration of symptoms and need longer to recover. The question is: What if the potential for brain damage is higher in even younger children?

Still, the guidelines will go a long way to ensuring better care of youngsters with concussion. “Adolescent and childhood injuries don’t get near the awareness that they probably should,” Dr. Giza says. “In professional and Division I collegiate sports, they have a bully pulpit in the media. But there are many more high school, grade school and Pop Warner football players out there – probably millions – compared with about 2,000 NFL players. It’s time to focus more of our attention in brain-injury research where the numbers are.”

Freelance writer Shari Roan wrote about medicine and healthcare for the Los Angeles Times.

 

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