FEATURE — Winter 2006

Terrie E. Inder is associate professor of pediatrics, of radiology, and of neurology at the School of Medicine. Her research shows that magnetic resonance imaging (MRI) scans can determine abnormalities in the gray and white matter of the brains of very pre-term infants, those born at 30 weeks or less, and this has implications for diagnosis and early treatments.

A Big Devotion for the Smallest Lives

Associate Professor Terrie Inder uses MRI scans of premature infants' brains to predict future developmental delays and to suggest early interventions.

By Diane Duke Williams

When Teo Carasso was born 10 weeks early, his skin was translucent, he weighed as much as a small sack of sugar, and he was so tiny that his mom could slide her wedding ring to the top of one of his arms.

"Yet, each tiny part of him was perfectly formed, and his eyes were bright sea blue," says Sophie Carasso of Melbourne, Australia. "To me, he was the most beautiful little baby in the world."

For the first four months of his life, Teo struggled each day to survive. He was on a respirator for part of the time, he had a dangerous intestinal problem that required two surgeries, and he suffered numerous infections.

His parents also found out that Teo had significant bleeding in his brain. When he was born, they had enrolled him in a study led by Terrie E. Inder, associate professor of pediatrics at the School of Medicine, that, for the first time, used magnetic resonance imaging (MRI) to look inside premature babies' brains to predict problems they might have.

"We began numerous therapies as soon as Teo was released from the hospital in order to stimulate his brain and maximize his potential," Sophie Carasso says. "These therapies also helped us find practical solutions to issues raised when living with a special needs child. I don't believe Teo would be capable of doing many of the things he now does without this early intervention, and enrolling him in the study was one of the best decisions we've ever made."

When a baby is born early, one of the biggest questions among parents and health-care providers is whether this tiny infant will survive and whether it will lead a life that society considers normal. In the past, families and clinicians didn't know which of these babies could benefit from early interventions, such as physical, occupational, or speech therapy.

In a study published August 17, 2006, in the New England Journal of Medicine, Inder, along with pediatric researchers in New Zealand and Australia, discovered that magnetic resonance imaging (MRI) scans could determine abnormalities in the gray and white matter of the brains of very pre-term infants, those born at 30 weeks or less. Following the infants until their second birthday, Inder and her colleagues graded these abnormalities and were able to predict the risk of severe cognitive delays, psychomotor delays, cerebral palsy, or hearing or vision problems that may be seen in children by age 2.

"These findings are a breakthrough because previous technology—cranial ultrasounds—do not show abnormalities in infants' brains," says Inder, also associate professor of radiology and of neurology. "We now understand that being born prematurely significantly affects structural brain development, and that has implications for a baby's risk of learning problems."

The brain is made up of two major sides, and within each side is the gray matter and the white matter. The gray matter acts as a computer hard drive of sorts and sends information over the white matter, which is simply the cabling network of the brain. But in the brain of premature infants, the cabling is not insulated and is much more likely to be injured.

Lesions on these cables essentially disconnect the hard drive from the rest of the network, hampering the brain's ability to rapidly send messages to muscles, nerves, and other parts of the body.

As a result, 50 percent of premature infants have trouble crawling, walking upright, running, swinging their arms, or performing other activities that require coordination and balance. Recent research also shows that 5 percent to 15 percent of premature infants who survive have cerebral palsy, severe vision or hearing problems, or both, and 25 percent to 52 percent have cognitive, behavioral, and social difficulties that require special education.

Early rehabilitation, Inder says, can force the brain to reconnect and function again. "That's why we don't want to miss that window of opportunity," she says. "It's much harder to get the brain to reconnect when a child is 3 years old, and you'll never get the same results."

Inder also acknowledges that she and her colleagues provide guidelines—not absolutes—in their predictions to families. But it has been her experience that giving a family more knowledge about the brain and a baby's risks empowers them.

"Parents have been through three or four months of sitting in a neonatal intensive care unit watching their baby go through so much, and they want the best advice," she says.

Since the 1970s, when the National Institute of Child Health and Development was established, major advances in neonatal care have been made to improve survival in premature babies. These advances have focused on lung and heart disease in these tiny infants. But while completing fellowships in pediatrics and in neonatology, Inder was struck by how little physicians and researchers know about the brains of premature babies.

During a fellowship in 1996 at Harvard University, one of Inder's colleagues was using MRI to determine what was normal in babies' brains. Inder decided that MRI also could provide a window into premature babies' brains. "I wanted to understand what was going wrong, when it was going wrong, and what they meant to the baby," Inder says.

Neuropsychologist Peter Anderson, another researcher on the study published in the NEJM, says Inder is extremely passionate about sick newborns. "She has endless clinical questions that she wants to investigate," says Anderson, co-director of the Australian Centre for Child Neuropsychological Studies at the Murdoch Children's Research Institute in Australia. "Working with her is exciting as there is never a shortage of important research projects."

Inder, a native of New Zealand, knew from a young age that she wanted to be a physician, but her parents were leery of her career plans. Her father, who mostly attended technical colleges, owned a construction company, and her mother left school when she was 13.

"They weren't sure about me going into medicine," Inder says. "They thought it was a very ambitious goal."

She focused on family medicine, emulating her own family's physician, as she went off to a seven-year medical program at the University of Dunedin in New Zealand. She discovered, however, during her final years of medical school that she liked research and wanted to specialize in pediatrics. After a pediatric residency, she decided that she wanted to take care of newborns and enjoyed the applied physiology and chemistry necessary for working in a neonatal intensive care unit (NICU).

"It's easy to stay up late at night writing grants and papers when you're driven every day by going into the NICU and seeing the little babies that really need us to advocate and find the answers so we can improve their lives," Inder says.

"It's easy to stay up late at night writing grants and papers when you're driven every day by going into the NICU and seeing the little babies that really need us to advocate and find the answers so we can improve their lives," Inder says.

Inder hopes her research will establish a standard of care in which all premature babies receive an MRI when they're born. She also plans, in the near future, to establish a Center of Excellence at the School of Medicine in collaboration with her Washington University research colleagues, Jeffrey Neil, the Allen P. and Josephine B. Green Professor of Neurology; David Van Essen, the Edison Professor of Neurobiology; Amit Mathur, associate professor of pediatrics; and Robert McKinstry, associate professor of radiology. The center will aim to improve neurological outcomes for babies at risk—those born prematurely and those born full term with any complications that could affect their brains.

"I want to set up the center, have it shine like a beacon, and be here for a long time," says Inder, who moved a year ago to St. Louis with her three children.

Alan L. Schwartz, the Harriet B. Spoehrer Professor and head of the Department of Pediatrics, says Inder has devoted her career to defining the basis of normal brain development in the smallest premature infant and the abnormalities in many disease states. "She wisely uses all of the various approaches available—her superior clinical skills to the cutting-edge technology of advanced MRI to health-outcome analysis," he says. "Her latest study in the NEJM underscores her approach. We and tomorrow's children are most fortunate in having Dr. Inder at the Washington University School of Medicine."

Inder has continued to follow Teo Carasso in other studies and consult with his family about his progress. He now is a healthy, happy 5-year-old with a vibrant personality. He has some special challenges—he is visually impaired, has mild cerebral palsy, and an autism spectrum disorder. But he also reads well above his age level; loves letters, numbers, and dates; and enjoys playing with his 3-year-old brother, Eli.

Sophie Carasso says working with Inder is an incredible privilege. "Her knowledge gave us the ability to pre-empt what was ahead, allowing us to contemplate the best course of action and then mentally and physically prepare to face the challenges for both Teo and our family. She is the most extraordinary woman whose work and research have directly affected my family's life," she says.

Diane Duke Williams is a free-lance writer based in St. Louis.