The Clock Strikes Early: How Premature Birth Affects Brain Development
Source: MedlinePlus
When expecting a baby, every parent hopes for a happy, healthy child. But for a growing number of families, that journey begins with unexpected challenges. Premature births (infants born before 37 weeks of gestation) are on the rise. In 2023, 8.3% of all births in Canada were premature, the highest rate observed in 50 years.
Premature birth does not just result in visible physical differences, such as general small stature or delayed physical growth; it may also influence how the brain functions later in life. While advances in neonatal care have significantly improved long-term physical outcomes – helping many preterm infants achieve typical growth and development over time – premature birth can interrupt key stages of brain development that occur in the final weeks of pregnancy. These disruptions may have lasting effects on cognition.
Recently, a team of researchers at Western University, led by Dr. Emily Nichols and Dr. Emma Duerden with contributions from Dr. Ali Khan, set out to explore how premature birth impacts brain development during infancy. They focused specifically on the hippocampus, a brain region known for its involvement in learning and memory. The hippocampus is made up of several subfields, including the cornu ammonis (CA1-4), the dentate gyrus, and the subiculum; each supporting a unique aspect of learning and memory. These regions are structurally distinct from one another, maturing at different rates and showing diverse vulnerabilities to stress, injury, and disease.
Using MRI scans from over 500 newborns, including 120 born preterm, the team examined two structural components of each hippocampal subfield: volume and myelination. Volume reflects overall size, whereas myelination refers to the formation of myelin, a fatty substance that coats neurons. In the same way that electrical wires are coated with insulation to help current flow efficiently, myelin acts as an insulating layer around neurons, allowing signals in the brain to travel quickly and reliably. Critically, measuring volume helps the researchers evaluate whether the subfields are growing at a typical pace, while assessing myelination provides insight into how efficiently these regions can communicate.
To analyze these images, the researchers used HippUnfold, a computational tool developed in Dr. Khan’s lab here at Western. HippUnfold automatically extracts structural features of the hippocampus and each of its subfields from an MRI scan, making it possible to process large datasets efficiently with minimal error. Originally designed for adults, the team adapted the program to work with newborn scans. Premature infants were scanned soon after birth and again at around 40 weeks – the equivalent age that a full-term baby would typically be born. They compared volume and myelination at these two time points with infants that were born full-term.
They found that hippocampal volume “caught up” over time; by 40 weeks, preterm infants’ hippocampal size was similar to that of full-term infants. Myelination, however, did not. At birth and even at 40 weeks, preterm infants showed significantly lower levels of myelin in their hippocampus. Interestingly, not all areas were equally affected – subfields that are naturally less myelinated (like CA1 and CA2) were more vulnerable, while others (like CA3) were more resilient.
The researchers also sought to determine which factors best predicted these outcomes. They found that accounting for time spent inside versus outside the womb separately, rather than just the infant’s total age since conception, was the better predictor of myelin content. In contrast, both measures equally predicted volume. This suggests that the stress of premature birth has a significant impact on brain development, specifically that the time spent in utero plays a critical role (at least for myelination) that cannot be compensated for after birth.
You might be wondering: why does this matter? Abnormalities in hippocampal myelination have been linked to conditions in adulthood like schizophrenia, bipolar disorder, and memory impairments. While the physical challenges of prematurity are often visible but well-managed, its cognitive and neurological effects may be more subtle yet long-lasting. Interventions may also be needed to support and improve cognitive outcomes, including cognitive training exercises, therapy, and possibly even medications.
Nonetheless, premature births are becoming more common, and several factors may contribute. One plausible explanation is the trend of delayed parenthood, as the risk of premature birth increases as women get older. Economic and social pressures driving the need for living in a two-income household or the desire to establish a career before starting a family are pushing women to have children later in life than ever before. In 2023, one in four new mothers in Canada were aged 35 years or older, compared to just one in ten reported 30 years ago. Other factors, including medical conditions, multiple pregnancies, and lifestyle choices (e.g., poor nutrition, chronic stress, smoking), can also play a role.
Although this study did not specifically investigate the reasons for prematurity directly, it raises important questions about the factors that families can control. Being aware of these risks may help prospective parents make informed decisions, but societal support may also be needed to give them the options and resources to do so. Providing that support could be just as crucial for healthy brain development as any medical breakthrough in neonatal care.
Original Article: Nichols, E.S., Karat, B.G., Grace, M., Bezanson, S., Khan, A.R., & Duerden, E.G. (2025). Early life stress impairs hippocampal subfield myelination. Communications Biology, 8, 785. https://doi.org/10.1038/s42003-025-08165-x