Portions of brain are smaller in children born prematurely

Genetics, hormones may shield girls’ brains from adverse effects of early birth

Kids on a playground can be hard to tell apart. But those who were born significantly preterm may be struggling with a hidden handicap that sets them apart from their peers: specific areas of the brain that are smaller than normal, even years later.

A collaborative study between the Stanford, Yale and Brown medical schools compared the brain volumes of two types of 8 year olds: those born prematurely and those born full-term. The researchers found significant, lingering reductions in the areas of the cerebral cortex responsible for reading, language, emotion and behavior.

Even more surprising, the researchers discovered that the brains of preterm boys were more severely affected than were girls.

“It’s fascinating,” said Allan Reiss, MD, the Howard C. Robbins Professor of Psychiatry and Behavioral Sciences. “It’s as though we’re seeing echoes of the ‘big bang’ of preterm birth at 8 years of age.”

Reiss is the director of the Stanford Psychiatry Neuroimaging Laboratory and co-director of the Center for Brain and Behavior at Lucile Packard Children’s Hospital.

Doctors have known that preterm newborn boys fare more poorly than girls, but it’s not been clear why.

The differences persist even after the early medical hurdles have been cleared: preterm boys struggle more than preterm girls with speech and language and have a harder time in academic and social situations as they grow older.

Although it stands to reason that newborns making an unreasonably early appearance have smaller brain volumes than full-term babies, it wasn’t known that boys’ brains are more severely affected or that the disparity persists for so long.

“Smaller brain volume has never been specifically related to increased risk of adverse outcome in males as opposed to females,” Reiss said. “This is a striking and significant developmental abnormality in males who were born preterm.”

Reiss and Stanford co-investigator Shelli Kesler, PhD, collaborated with Laura Ment, MD, Betty Vohr, MD, and colleagues at Yale and Brown to compare brain-imaging data of 65 preterm children to 31 healthy, full-term children. Preterm babies were born at around 28 weeks of gestation and weighed about 2 pounds at birth.

The study was published in the August issue of the Journal of Pediatrics.

“In the preterm group as a whole, we found the volumes of both grey matter and white matter were reduced,” said Reiss. “When we divided the preterm group by gender we found, bingo, the females had normal or preserved white matter volume, but the males’ volumes were reduced compared to their full-term peers.”

White matter is primarily made up of the axon connections and cells that facilitate communication between parts of the brain over distances, whereas grey matter consists of the cell bodies of the brain’s nerve cells, where signal processing and thinking happen. White matter lesions are responsible for the symptoms of multiple sclerosis, which compromise both mobility and cognitive functions.

“The adverse effects of preterm birth, such as hypoxia, expose the premature brain to an environment it’s not yet supposed to be in,” said Reiss. “Researchers have hypothesized that white matter might be preferentially affected, but sex-based differences have never been clearly shown until now.”

Reiss speculates that girls may gain a measure of protection either through genetics or hormones.

“Unlike boys, girls have two X chromosomes, giving them a layer of partial genetic redundancy that may help protect against the effects of preterm birth,” he said. “It’s also very possible that differences in hormone levels between boys and girls before and after birth may play a role.”

The researchers also looked at which specific white matter areas are most compromised by preterm birth.

“We found that certain parts of the brain were more vulnerable to the effects of preterm birth than others,” Reiss said.

“In males, the temporal lobe and the deep cerebral region of the brain are preferentially affected,” he added. “This is very interesting, because it turns out that individuals who are born preterm often have particular problems in language-based areas, and the temporal lobe is one of the seats of language.”

These areas are also involved in many other important functions, including emotion, attention and reading – classic Achilles heels for many kids born preterm.

Reiss said the study indicates that researchers should consider trying to develop a way to stimulate white matter growth in the brains of preterm babies. He said they could also explore developing an agent that would help protect infants’ brains from the effects of premature birth.