In Simple Terms
A baby’s brain grows rapidly in the final months of pregnancy. When a baby is born early, that growth continues in a very different setting, and some parts of the brain may develop along a different path—not simply more slowly. Researchers found that changes in the cerebellum were linked to differences in movement, language, and thinking skills in early childhood.
A Rapid-Growth Window in Late Pregnancy
The cerebellum undergoes major changes during the final trimester of pregnancy. Between 24 and 40 weeks of gestation, it grows to about five times its earlier size. During this period, granule cells multiply and move into position, while the branches of another type of neuron, called Purkinje cells, develop. The organization and connections of these cells help build circuits involved in movement and coordination, as well as language and thinking.
When a pregnancy reaches term, this stage of development takes place inside the womb. If a baby arrives early, brain growth continues after birth in a different environment, which may include a neonatal intensive care unit and the clinical conditions, sensory experiences, and possible physical stress that come with it. This comparison does not mean that every infant has the same experience in intensive care. It highlights that developing brain tissue faces circumstances different from those it would have encountered had the pregnancy continued.
The cerebellum matters for more than controlling movement. The coordinated development of its circuits contributes to a wider range of functions, helping explain why some children born early have challenges with balance, fine motor skills, language acquisition, or learning. These difficulties do not always occur alongside a major, clearly visible brain injury, which has made them challenging for doctors and researchers to explain.
From Brain Scans to Maps of Cells
To investigate the question, a research team from Children’s National Hospital in Washington and Seattle Children’s combined two types of human data. The researchers followed 176 infants born prematurely, using brain imaging and tracking their development during the first years of life. They also examined postmortem cerebellar tissue samples from 83 infants, including babies born early and others born at term.
Clinical follow-up went beyond measuring the brain’s shape. The team assessed neurodevelopment at 9, 18, 24, and 36 months of age. This allowed the researchers to compare images and measures of cerebellar size with children’s skills at several stages, rather than relying on a single snapshot.
The tissue samples underwent spatial gene-expression analysis. This method measures gene activity while preserving information about where each cell sits within the tissue, rather than separating the cells from their locations. The researchers focused on two main cell types: granule cells, which are among the most abundant cells in the brain, and Purkinje cells, which play a central role in the cerebellar cortex’s output and connections.
The work was led by two co-first authors, Georgios Sanidas and Gabriele Simonetti, as part of a collaboration involving the Center for Neuroscience Research and the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National Hospital. Panagiotis Kratimenos and Vittorio Gallo helped oversee the research, alongside colleagues at the participating institutions. By combining data from living children with human tissue collected after death, the team could connect visible patterns of development with changes taking place at the cellular level.
Not Just a Delay on the Same Path
The findings suggest that premature birth is associated with a shift in the cerebellum’s developmental path, rather than merely a slowdown along the usual route. The researchers found signs that granule cells may remain immature and that the structural refinement of Purkinje cells does not proceed in the same way as it does at comparable stages of development. Differences between these two cell types suggest that parts of the developing system do not progress in sync.
Put simply, the cerebellum may not just need extra time to grow. After premature birth, some cells may develop in a different biological state. As a result, two children at the same age after birth—or at the same stage relative to pregnancy—may follow different patterns of maturation, depending on the conditions at the start of their lives. The study describes this as a shift in the timing of biological maturation, not simply a delay that can be measured by the calendar alone.
This finding may help explain a clinical puzzle: a child can have difficulties with movement, language, or executive skills even when scans do not show a focal bleed, lack of oxygen, or obvious structural lesion that fully explains them. Some differences may also arise from how circuits and cells form during a sensitive period, rather than from a single major injury that is easy to see on imaging.
The study does not suggest that every child born prematurely will face the same difficulties, or that any child’s developmental path is predetermined. Its findings describe patterns and associations across groups of children and tissue samples; they do not erase the differences between individuals. But they challenge the idea that simply allowing time to pass will always bring the brain back onto the path it might have followed if pregnancy had continued.
230 Cubic Millimeters for Every Week
In the imaging data, each week an infant spent developing outside the womb before reaching full term was associated with an average reduction of about 230 cubic millimeters in cerebellar volume. To give readers a rough visual comparison, the study summary described this amount as about the size of a pea. The figure reflects a statistical relationship between time spent developing outside the womb and cerebellar volume; it cannot be used to predict an individual child’s outcome.
When the children were between 9 and 36 months old, smaller cerebellar volume was associated with notable delays across several areas. These included gross motor skills, such as movement and balance, fine motor skills, expressive and receptive language, and cognitive executive functions. The associations do not mean that cerebellar size alone explains every difference in development. They do, however, reveal a connection between structural growth and some assessment results in early childhood.
The 230-cubic-millimeter measurement matters because it gives researchers a way to compare the relationship between birth timing and cerebellar growth across the data. But it should not be interpreted as a certain, fixed loss for every infant in every week, or as a complete description of a child’s abilities. The team also found that factors beyond gestational age at birth may affect how quickly the cerebellum grows after birth.
The Clinical Environment Matters, Too
According to the study, gestational age at birth provides an important starting point for the path of molecular maturation, but it is not the only influence. Systemic illness, physical stress, and some aspects of care in the neonatal intensive care unit may affect the rate of cerebellar growth. Children’s outcomes are therefore not determined by a single factor, and the experience of care after birth may modify a path that began with premature delivery.
It is important to distinguish describing an effect from proving that a particular practice causes harm or protects the brain. The findings indicate that the clinical conditions surrounding an infant are associated with differences in growth. They do not amount to a general judgment about every treatment practice, nor do they mean that intensive care itself explains all the differences. Infants need medical support; the research aims to understand how that support can be tailored to their developing brains.
Spatial gene-expression analysis is valuable because it offers a view of differences that brain scans alone cannot reveal. Imaging can measure volume or show overall structure, while maps of gene activity help researchers ask what is happening inside the cells: Have they matured? Have their branches developed? Are different cell types progressing in step? Combining these approaches gives researchers a broader understanding, without making either one a substitute for the other.
Toward Care That Considers Maturity, Not Just Age
The findings raise a practical question for neonatal medicine: Is it enough to assess a child’s development by the time elapsed since birth, or should clinicians also consider biological maturity? The researchers suggest that follow-up for children born prematurely may benefit from taking the brain’s stage of development into account, rather than relying on chronological age alone. The aim is to improve estimates of risk and time interventions to suit a child’s developmental state.
The molecular markers now being identified could eventually help researchers estimate maturity or classify risk more precisely. But this remains a research possibility, not a diagnostic tool ready for clinical use based on the information available about the study. Moving from identifying a marker in research data to developing a reliable test—and then using it to guide treatment—requires further validation.
The team is currently testing compounds intended to protect neurons, alongside improved clinical protocols designed to support networks of granule and Purkinje cells during sensitive periods. The researchers’ stated goal is to preserve cerebellar growth and improve developmental prospects, not to claim that a particular treatment has already been proven effective. The research was supported by the Raynor Cerebellum Project Foundation.
This approach matters because it shifts attention from treating the cerebellum as a single mass measured by its size to understanding it as a system whose different cell types change on different timelines. If researchers can reliably identify the biological stage of each child’s brain, it may become possible to design more precise treatment studies and compare the effects of care during periods when cells and circuits are especially open to influence.
The Bottom Line
The study published in Science offers evidence that premature birth may change the cerebellum’s developmental path, rather than simply slow it down before the brain catches up on its own. The researchers combined imaging and follow-up data from 176 infants with spatial analysis of cerebellar tissue from 83 infants, finding differences in the maturation of granule cells and the development of Purkinje cells. Each week of development outside the womb before full term was associated with about 230 cubic millimeters less cerebellar volume, as well as differences in movement, language, and executive skills between 9 and 36 months of age.
These findings do not determine the future of every child born early, and they do not prove that smaller cerebellar volume alone causes every developmental challenge. Instead, they refocus the scientific question: not only how much the brain has grown, but how its cells matured and under what conditions. As researchers continue to test potential markers and protective interventions, this perspective may help guide care that better accounts for biological differences among children—and deepen understanding of the cerebellum’s sensitive period of growth after premature birth.