Yale researchers have found differences in the fetal brains of babies to be born prematurely, suggesting that doctors can identify those at risk of future neurological disorders before birth to achieve better long-term health outcomes.

A collaboration between researchers at Yale and Wayne State University, the study is the first to show that altered neural system activity associated with babies born preterm — before 37 weeks — is present in utero. The researchers analyzed functional magnetic resonance imaging data from 32 fetuses and published their findings in Scientific Reports on Jan. 9.

“We found differences in functional connectivity in brain regions that are later responsible for language,” said Dustin Scheinost, a professor at the Yale School of Medicine and a co-author on the study. “What is impressive about these findings is that they foreshadow similar differences that we observe in preterm infants, children, adolescents and young adults.”

Currently, scientists are uncertain whether cognitive impairments and brain differences associated with preterm birth are due to complications of being born too early or are part of a developmental disorder starting before birth. Recent fMRI advances have just made these types of studies in fetuses possible, according to Scheinost.

The researchers used fMRI data collected from healthy fetuses at the start of the third trimester, some of which were enrolled for their high risk of early delivery, according to Moriah Thomason, a Wayne State University professor and lead author on the study. Of the 32  fetuses studied, 14 were later born preterm.

The study also drew from data from more than 100 typically developing fetuses to use as comparison subjects, added Moriah Thomason, a Wayne State University professor and the lead author on the study.

After the babies were born, data for those born prematurely were compared to those born full-term to see if well-known differences in the functional organization of the brain associated with preterm birth were present while in utero.

“We measured brain signals using MRI and then looked for spatial and temporal patterns in the fluctuations between different regions in the brain,” Scheinost explained. “For example, if two remote brain regions show a high synchrony in their brain signals, we would say these regions are functionally connected and are likely involved in similar cognitive or neurological processes.”

The researchers calculated the functional connectivity for each fetus and compared across the study groups. Through this analysis, the scientists found that premature babies not only show alterations in language areas from birth through young adulthood, but that these differences are observable even before birth. In particular, the functional connectivity of a language region in the left hemisphere of the brain was reduced in fetuses that would subsequently be born preterm.

Additionally, the study examined the connection between strength of functional connectivity in the brain and gestational age at delivery, finding that the neural systems of the babies born closer to the expected due date were more similar to those of the control group.

These findings are significant, Schienost said, because they demonstrate that brain differences in babies born prematurely can be independent of the many complications of being born too early.

According to the researchers, the data suggest  that neurological diseases typically associated with premature delivery, such as autism and ADHD, may come from pre-existing in utero neurological conditions.

“A better mechanistic understanding of the brain injuries of prematurity can help to inform interventional strategies,” Thomason said.

The researchers hope to continue to study both normal development of the fetal brain through the third trimester and how environmental perturbations — such as prenatal stress and preterm birth — alter brain development, said Scheinost.

The study’s results also serve to support more investigation into the efficacy of prenatal neurobehavioral therapy as a neurological intervention. For example, prenatal exposure to complex sounds may strengthen the development of the neural network for information processing after birth, according to the paper.

“The ability to identify those most at risk of later neurological injury can inform individual treatment strategies to achieve the best outcome within an individual,” Thomason said.

In 2015, about 10 percent of infants born in the U.S. were premature, according to the Centers for Disease Control and Prevention.