A study suggests that premature birth disrupts the maturation of the cerebellum

This work is excellent, as it defines the developmental architecture of the cerebellum in both normal conditions and in cases of preterm birth. This means that they have succeeded in mapping how biological tissue is organised, interacts and develops over time. Furthermore, they have discovered that in preterm birth there is an asynchrony in the maturation of cerebellar neurons relative to gestational age, which represents the first step towards designing therapeutic approaches to intervene in this process.

However, the fact that these differences persist until the age equivalent to full term does not mean that they are permanent; it is not yet known whether they will continue, diminish or be compensated for in the future.

This is a robust study showing that gestational age at birth has a lasting impact on the maturation of the cerebellum in preterm babies. The cerebellum contains the majority of the brain’s neurons and, through its connections with the rest of the brain, modulates everything from movement to language and social behaviour. Generating and wiring so many neurons requires a very prolonged development process, from the first weeks of gestation until around two years after birth, which makes it particularly vulnerable. Its growth peaks in the final trimester, precisely when premature births occur. We knew that being born prematurely disrupts its development and is associated with motor and cognitive difficulties, but we did not know what was happening at the cellular level.
 
The authors combine brain imaging and follow-up of a large cohort with post-mortem tissue analysis using gene expression maps and artificial intelligence, and both approaches show that this signature is observed primarily in two types of neurons. Purkinje cells—the main neurons of the cerebellar cortex—do not reduce their density or refine their connections as they do in full-term infants. Granular cells – the most numerous neurons in the entire brain – remain immature for longer, particularly in the most premature infants. As both cell populations depend on one another to form the cerebellar circuit, the findings suggest that, upon reaching the age equivalent to full term, the cerebellum of a premature baby may follow a different course of maturation, even though its structure appears relatively normal.

There are several limitations. Part of the analysis is based on a small number of post-mortem samples, which may not necessarily be representative of survivors. Furthermore, the data are correlational and do not allow the effect of prematurity to be separated from that of its common complications, such as inflammation or oxygen deprivation. A recent study by the same group in mice, published in Brain, suggests that both complications leave distinct marks on the cerebellum and on behaviour. Nor do we know whether these differences persist into childhood or whether the brain compensates for them over time, so we cannot yet draw long-term conclusions. 

Although it is still too early to translate these findings into clinical practice, the study invites us to look at prematurity in a different light. A preterm baby not only completes the third trimester of gestation outside the womb, but may also follow a different course of brain maturation. If future research confirms this, knowing the degree of maturation of their cells could complement corrected age in guiding follow-up care and, later on, help to assess the appropriate time to administer neuroprotective treatments.

Prematurity can affect different regions of the brain, not just the cerebellum. However, the fact that this study has identified alterations in cerebellar circuits is particularly significant, as there is growing evidence that perinatal alterations in the cerebellum may influence the circuits to which it is connected. Thus, its effects could extend to other areas, such as the cerebral cortex, and amplify the impact of prematurity on the development of motor, cognitive or linguistic functions. This possibility still needs to be investigated, but it reinforces the importance of studying how brain circuits assemble and communicate, both during normal development and under pathological conditions. Understanding these processes will help to better explain the consequences of prematurity and guide future interventions.