HMN 2026: What extremely preterm birth teaches us about the brain

Extremely preterm birth (before 28 weeks of gestation) places infants into the world at one of the most extraordinary moments in human development. The brain at this stage is not simply growing; it is folding, organizing, and laying down the networks that will eventually support language, memory, attention, and learning. It is doing all of this in the dark, in the warmth, protected. When birth happens this early, all conditions change in an instant.

Modern neonatal medicine has achieved something remarkable: More of these children survive than ever before. But as clinical doctors and researchers in this field, we also know that survival is only the beginning of the story.

Looking at brain scans side by side of children born months too soon, and their peers born at full term, the differences were subtle at first glance. But the more we looked, the more they revealed. Not a single dramatic gap, but a quiet, system-wide story written into the architecture of the brain itself.

A window disrupted

The third trimester is, in many ways, one of the brain’s most ambitious phases. Its surface expands rapidly and folds into the ridges and grooves familiar from anatomy textbooks. But those folds are not cosmetic. They reflect an underlying organization of neural networks, the scaffolding of future thought.

When an extremely preterm infant enters the world, that scaffolding is still being built. The brain is suddenly exposed to an environment it was never designed to encounter at this stage. The noise, light, and necessary interventions—none of this is what the developing brain expects. Development continues, but on an altered course. At the same time, the infant is deprived of natural stimuli such as kicking the walls of the mother’s womb and hearing the mother’s voice.

Our study, now published in NeuroImage, set out to understand the consequences of that altered course. We followed children born extremely preterm and compared them with peers born at term. At around age 10, we examined detailed features of brain structure, and at age 12, we assessed cognitive performance.

What the brain told us

The structural differences we found were not confined to one region. Children born extremely preterm showed a thinner cortex, less folding, and shallower sulci (i.e., the grooves between brain folds) compared with their term-born peers. These differences were most evident in temporal and cingulate regions; areas closely related to language, memory, attention, and cognitive control.

But perhaps the most important finding was that no single measure told the full story. It was not one region or one feature that mattered most, but the overall pattern, the way multiple features came together across the brain. The brain does not function in isolated parts. It operates as an integrated system, and it was the balance across that system that appeared to shape later cognitive ability.

When networks fall out of sync

Perhaps the finding that struck us most was not about structure at all, but about communication. Among children who went on to experience cognitive difficulties, we observed something unusual—altered connectivity between frontal, cingulate, and temporal regions. In some cases, these regions showed anticorrelated patterns essentially moving in opposite directions when they would normally move in concert. Imagine a soccer team where the main players are not only out of position but pulling in different directions. That is something like what we found at the neural level. The parts of the brain that should be working together were, in some children, less coordinated and almost out of sync.

We also found differences in the brain’s hubs, the highly connected regions that act as coordination centers, integrating information from across the network. In children with cognitive difficulties, these hubs were positioned differently compared with those who developed within the typical range. Even a subtle shift in where those coordination centers sit can affect how efficiently the whole system processes and shares information. What this tells us is that outcomes after extremely preterm birth are not simply determined by what happened at birth. They are shaped by how the developing brain reorganizes itself in the months and years that follow.

Can we intervene earlier?

This is the question we keep returning to. Our findings suggest that patterns of brain structure and connectivity may one day help identify children at higher risk of cognitive difficulties before those challenges appear in the classroom. The goal is not to label children, but to open a window for earlier and more timely support.

The brain regions most affected in our study are those associated with language, attention, and working memory. These are capacities that can be strengthened through targeted educational strategies, cognitive interventions, and early developmental support. We also found that children with more severe neonatal complications, such as prolonged need for ventilation or bronchopulmonary dysplasia, were more likely to show later cognitive difficulties. This reinforces how important it is to continue improving the quality of neonatal intensive care from day one.

The resilience that surprised us

We want to end with the finding that, honestly, moved us the most. Not all extremely preterm children showed disrupted connectivity. A substantial number in our cohort performed within the typical cognitive range at age 12. Their brains showed some structural differences compared with term-born peers, but they did not show the altered connectivity patterns we saw in children with cognitive difficulties. That variability is not noise. It is one of the most meaningful things we found. It tells us that the developing brain is not simply a record of what went wrong. It is, in many children, a record of what held together.

Real, measurable, neural resilience is common among children born extremely preterm. Understanding what protects these children, whether biological, environmental, or a combination of both, is now just as important to us as understanding the risk. Because the question is no longer only what changes in the preterm brain. It is also what protects it.

This story is part of Science X Dialog, where researchers can report findings from their published research articles. Visit this page for information about Science X Dialog and how to participate.

The content is provided for information purposes only.