Early Birth, Altered Brain Connections

Ten years ago, I gave birth to my first child. He was born at 31 weeks gestation—almost two months early—and spent his first five weeks of life in the neo-natal intensive care unit until his heart and lungs were strong enough to function on their own. His story is not uncommon. The World Health Organization estimates that nearly 15 million babies are born before term each year. Premature birth is linked to a variety of health problems—including a higher risk of neurological and psychiatric issues like autism, attention deficit hyperactivity disorder (ADHD), and anxiety disorder. Research presented at Neuroscience 2015 in Chicago suggests such increased risk for brain-related disorders may be due to changes in critical circuits seen both at and before birth in premature babies.

Differences in white matter tracts

Past research has shown that the brain does quite a bit of maturing over the last few weeks of gestation, says Cynthia Rogers, a child psychiatrist and neurologist at the Washington University School of Medicine in St. Louis and a Dana Foundation grantee.

“What you see in these last few weeks of gestation in typical development is that the brain enlarges and becomes more complexly folded,” she said. “But if you were born early at the twenty-seven week mark, the brain does not look like the full-term brain even when you scan it at forty weeks [full term]. So we wondered if that altered brain development might be linked to the increased risk of ADHD, autism, and anxiety that we so often see in preemies.”

To test the idea, Rogers and her colleagues used both functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI). They compared the brains of 58 babies born at full-term to 76 who were born at least 10 weeks before their due date—with the full-term infants scanned at birth and the preemies scanned at approximately 40 weeks. The researchers found significant differences in white matter tracts, the neural fibers that help different brain regions communicate across the brain. They also discovered altered connectivity in brain networks like the frontoparietal network, vital to attention and emotional processing.

“What we found is that preterm infants indeed have abnormal structural brain connections—where preterms had less coordinated activity or weaker connections in important brain networks,” said Rogers. “This indicates that prematurity is altering the structure and function of brain regions that are linked to the very childhood psychiatric disorders that these children are at a higher risk for.”

Connections in utero

Rogers’ findings beg the question:  Are such abnormalities present before birth?  Work in Moriah Thomason’s laboratory at Wayne State University School of Medicine suggests they might be—at least when it comes to motor development. Thomason, a translational neuroscientist, has been studying the brain and preterm birth in Detroit, the city with the highest incidence of premature birth and infant mortality in the United States. Like the increased risk for some childhood psychiatric disorders, preterm birth is also linked to delays in motor development.

“Our work suggests that these changes in the brain could be happening before these babies are born, before the extremely challenging situation of being born too early,” she said. “And we are able to study some of these brain changes by inviting pregnant women, both who are healthy and those who are at high risk for preterm birth, to come in for an MRI where we focus on the brain of the developing fetus.”

Thomason and her colleagues compared the in utero brain scans of 18 fetuses later born prematurely and 18 later born full-term who were matched for age, gender, and motion during the scanning session. They honed in on the brain’s motor regions, including the cerebellum, to see how they were connected to other brain areas.

“We knew from prior work in our lab that the strength of connectivity between brain regions does increase across fetal age,” she said. “But here we found that term fetuses had higher levels of connectivity in these motor regions than the preterms. And when we took a closer look at what was happening, we found those differences were really driven by distance. That is, it’s really the distant connectivity, or connections between regions that are further part in the brain, were we really see differences between these two groups, with weaker connections in the preterm babies.”

Continuing to follow

Thomason cautions she can’t say definitively that the differences observed before birth precipitate problems later in development. After all, some preemies grow up with no problems at all. She, like Rogers, plans to follow these children through toddlerhood and beyond to better understand how their particular brain differences might be linked to later developmental issues.

“We have quite a bit of exciting work ahead—and we’ll stay with these children to see if we can link back what kind of connectivity profiles went with the different types of behavioral outcomes in toddlers. We don’t know how far this will all go,” she said. “But the data supports the idea that the biology of the premature brain is different than of a full-term baby, even before birth. And that gives us opportunities to consider new therapeutics and interventions that could be done before these at-risk babies are even born.”

Certainly, preliminary work from Martha Welch’s laboratory at Columbia University suggests such early interventions, at least in a preemie’s first few weeks of life, can work. Her Family Nurture Intervention (FNI), a series of activities to promote development through directed family/infant interactions, has been shown to improve preterm infants’ developmental trajectories in some studies.  And future work may indicate ways to help strengthen brain connections even earlier.

Jay Giedd, moderator of the press conference in which both Rogers and Thomason presented, agrees. “More and more, we’re seeing that these brain connections are really important. And how the brain is connected is really what separates the old from the young, the male from the female, and the sick from the healthy,” he said. “We don’t know really how we can change these connections when we go awry yet. But we are starting to be able to measure these connections. And that’s the start. Once we can measure them, you can start to think about how you might intervene and make things better. Which makes this a really exciting time for this kind of research.”