20 May Karolinska Institutet Study Suggests Brain Folding Patterns at Age 10 Predict Cognitive Outcomes in Extremely Preterm Children
MedicalResearch.com Interview with:
Dr. Nivins
Samson Nivins, PhD
Department of Women’s and Children’s Health
Neonatology
Dr. Ådén
Ulrika Ådén, MD
Professor of Neonatology
Department of Women’s and Children’s Health
Karolinska Institutet
Stockholm, Sweden
MedicalResearch.com: What is the background for this study?
Response: Extremely preterm birth (before 28 weeks of gestation) accounts for a small but clinically significant proportion of all preterm births. Advances in neonatal care have significantly improved survival rates, and more of these children are now surviving into childhood and adolescence. However, many continue to face long-term challenges, particularly in cognitive development and academic achievement. What has been less well understood is why some extremely preterm children do well cognitively and others struggle, and whether these differences are reflected in the structure of the brain.
The third trimester of pregnancy is a critical window for brain development. This is when the brain undergoes rapid folding and surface expansion — processes that are abruptly interrupted when a baby is born extremely preterm. Our study set out to examine whether the brain’s folding patterns, measured at 10 years of age, differ between extremely preterm and term-born children, whether these differences predict cognitive performance at age 12, and whether children who develop cognitive difficulties show distinct patterns of brain organisation compared with those who do not.
MedicalResearch.com: What are the main findings?
Response: We found three main findings.
Extremely preterm children showed widespread differences in cortical folding at age 10 compared with term-born peers — including thinner cortex, lower gyrification, and shallower sulci, particularly in temporal and cingulate regions. These are brain regions involved in language, memory, attention, and cognitive control, and our findings suggest that the disruption caused by extremely preterm birth leaves a lasting imprint on the brain’s architecture well into mid-childhood.
Multivariate patterns combining multiple measures of cortical morphology — rather than any single measure — were associated with cognitive performance at age 12. This suggests that the brain’s overall structural organisation, rather than changes in any one specific region, is what matters most for cognitive outcomes.
Extremely preterm children who had cognitive problems showed distinctly different patterns of brain connectivity compared with those who performed within the typical range. Children with cognitive problems showed anticorrelations — essentially opposing patterns of co-variation — between frontal, cingulate, and temporal brain regions, suggesting less efficient integration of information across the brain. Their brain network hubs — the most highly connected regions responsible for coordinating cognitive processes — were also located in different areas compared with children without cognitive problems and compared with term-born children.
MedicalResearch.com: What might be done to help mitigate these findings?
Response: Our findings point to several directions.
The identification of multivariate brain patterns as early markers of cognitive risk raises the possibility of using neuroimaging at mid-childhood to identify children who may benefit most from targeted cognitive support before academic difficulties become entrenched. The temporal and cingulate regions most affected in our study are involved in language, working memory, and attentional control — domains directly relevant to school performance and potentially amenable to intervention.
Children with cognitive problems were more likely to have had greater neonatal illness — lower gestational age, longer periods on ventilators, and bronchopulmonary dysplasia. This highlights the importance of optimising neonatal care to reduce the severity and duration of early medical complications, as these appear to have lasting consequences for brain organisation. Early enriched developmental care programmes in neonatal intensive care units, designed to support brain development during the critical preterm period, may help mitigate some of these effects, although their long-term impact on cortical folding specifically remains to be established.
MedicalResearch.com: What recommendations do you have for future research?
Response: Several directions would meaningfully extend this work.
Longitudinal neuroimaging studies following brain structure from the neonatal period through childhood and adolescence are needed to understand how cortical folding trajectories evolve over time and whether early alterations predict later outcomes more reliably than mid-childhood measurements. Our study was cross-sectional at 10 years, which limits causal inference.
Larger multi-site studies would strengthen the generalisability of findings, as our sample was drawn from a single urban setting in Stockholm with relatively favourable neonatal outcomes. Replication in more diverse populations is essential to understand whether these brain and cognitive patterns hold across different ethnic and socioeconomic contexts.
Future studies should examine whether the distinct structural covariance patterns identified in children with cognitive problems are present earlier — at term-equivalent age or in early childhood — and whether they predict later outcomes. If confirmed, they could serve as early biomarkers for identifying children most at risk before difficulties become apparent.
Extremely preterm children are a highly heterogeneous population. Not every child struggles, and those who do, struggle in different ways and to different degrees. This heterogeneity calls for a shift away from group-level approaches toward individualised profiling — identifying which children are at risk, characterising the nature of their difficulties across multiple developmental domains, and tailoring support accordingly. Intervention trials that combine neuroimaging endpoints with cognitive and academic outcomes would be particularly valuable in this regard.
MedicalResearch.com: Is there anything else you would like to add?
Response: It is important to emphasise that our findings highlight lasting effects of extremely preterm birth on brain development — with the temporal and cingulate regions appearing most vulnerable — and equally underscore the remarkable resilience of many of these children. A substantial proportion of extremely preterm children performed within the typical cognitive range at age 12. Their brains, although structurally different from term-born peers in some respects, did not show the disrupted connectivity patterns observed in children with cognitive problems.
This heterogeneity is itself an important scientific message — extremely preterm birth is not a uniform experience, and understanding what protects some children is as important as understanding the risks.
Regarding disclosures: the study was supported by Tore Nilsons Stiftelse För Medicinsk Forskning, Märta och Gunnar Philipsons Stiftelse, and HKH Kronprinsessan Lovisas Förening För Barnasjukvård through a postdoctoral grant to Dr Nivins, and by the Swedish Brain Foundation and the Swedish Medical Research Council through a grant to Dr Ådén.
Citation:
Samson Nivins, Nelly Padilla, Hedvig Kvanta, Gustaf Mårtensson, Ulrika Ådén. Disrupted cortical folding and cognitive outcomes in extremely preterm children at mid-childhood. NeuroImage, Volume 335, 2026, 121993. https://doi.org/10.1016/j.neuroimage.2026.121993
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Last Updated on May 20, 2026 by Marie Benz MD FAAD