Premature Birth Alters Cerebellum Growth Along a Different Path, Study in Science Finds

A baby born early does not simply have a smaller version of a full-term brain waiting to grow into its due date. According to a study published in Science, the cerebellum of a premature infant, the structure that supports movement, language and cognition, develops along a different path than it would have inside the womb.

The finding speaks to a question that has bothered clinicians for years. Many children born prematurely go on to struggle with movement, language and learning, even when scans show no detectable brain injury. The older view held that preterm birth slows brain growth, and that these children catch up by their original due date and beyond. The new work challenges that idea.

The timing matters because of what normally happens between 24 and 40 weeks of pregnancy. In that window the human cerebellum goes through its fastest development, growing fivefold in size as its main neurons wire into complex communication networks. For a full-term infant, all of that happens in the protected environment of the uterus. For a baby born early, the same construction has to happen outside it.

The researchers found a measurable cost. Each week a baby spent outside the womb before reaching full term was associated with about 230 cubic millimeters less cerebellar volume, roughly the size of a pea. When children were assessed between 9 and 36 months of age, smaller cerebellar volume correlated with delays in movement, language and thinking skills.

Birth timing sets a baseline molecular program, the team reports, but it does not settle everything. Physiological stressors, illness and specific aspects of care in the neonatal intensive care unit significantly altered how fast the cerebellum grew.

The work was led by co-first authors Georgios Sanidas, MD, and Gabriele Simonti, of Children's National Hospital's Center for Neuroscience Research and the Sheikh Zayed Institute for Pediatric Surgical Innovation. They combined multiyear brain imaging and developmental tracking of 176 living infants with cellular analysis of existing brain tissue from 83 preterm and term infants. The tissue came from repositories including the NIH NeuroBioBank. Using spatial transcriptomics, which maps gene activity across intact tissue layers, they examined how Purkinje and granule cells, two major cerebellar neuron types, develop outside the womb compared with normal gestation.

Senior author Panagiotis Kratimenos, MD, PhD, a neonatologist and director of Research and the Neonatal Neurocritical Care Program at Children's National, said clinicians could always see the developmental differences but not the cellular machinery behind them. He described the combination of data from living participants and tissue samples as the source of a biological explanation. Sanidas said pairing the two let the team connect molecular programs set at birth to how children develop years later. Simonti added that the programs governing Purkinje and granule cells respond not only to birth timing but also to the clinical environment afterward.

Joint senior author Vittorio Gallo, PhD, who began the research at Children's National and continued it after becoming senior vice president and chief scientific officer at Seattle Children's, argued that preterm infants should be assessed and treated by developmental maturity rather than chronological age. He said the molecular markers could improve risk stratification, advance maturity biomarkers and help time neuroprotective therapies.

The team says it is now investigating targeted interventions based on the findings, aiming to steer the premature brain toward healthy maturation. Kratimenos described the goal as designing neuroprotective strategies matched to the biological state of a baby's brain cells in the NICU. The study was supported by the Raynor Cerebellum Project Foundation.