World Prematurity Day - Shedding Light on the BLACK BOX of Preterm Brain Development and Outcomes

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 Extremely preterm birth is one of the greatest challenges in neonatal health today. Every year, thousands of families face the uncertainty of seeing their tiny newborns survive against the odds, knowing that survival is just the first step in a long journey. 

A recent population-based study from Sweden led by Aden et al 2025 paints a striking picture, over the past two decades, survival rates for extremely preterm infants have improved a triumph of modern perinatal care. But despite this progress, neurodevelopmental outcomes, such as cognitive and motor function, have not improved in the same way (https://doi.org/10.1136/archdischild-2024-327919). This gap, often described as a ‘BLACK BOX’, leaves clinicians and researchers puzzled. Why does survival improve, but development remains stubbornly plateaued?

The answer is complex. Biological vulnerability e.g., the immaturity of organs, underdeveloped neural networks, plays a central role, but it is not the whole story. Environmental factors such as family stress, parental mental health, early stimulation, screen exposure, quality of caregiving, and broader community conditions etc. work together to shape early developmental trajectories. Recent study from Nivins et al 2025 shows that the biological impact of preterm birth on cognition is roughly twice that of genetic risk (e.g., polygenic scores), whereas socioeconomic factors account for another 30% of variability (https://doi.org/10.1001/jamanetworkopen.2025.4580). This still leaves nearly half of the differences in neurodevelopment unexplained, pointing to critical importance of neonatal experiences, medical complications, opportunities for early parent-infant bonding, and timely, targeted interventions that capitalise on periods of neuroplasticity. Disentangling the relative contributions and interactions among these factors is essential for designing interventions ranging from optimised NICU care and early therapy programs to family support and enriched home environments aimed at maximising neurodevelopmental outcomes and helping preterm children reach their full potential.

Furthermore, recent studies (Nivins et al 2025; Thalhammer et al 2025) reveal that preterm brains are astonishingly different. Children born at the same gestational age can have very different developmental trajectories, highlighting the limitations of a ‘ONE-SIZE-FITS-ALL’ approach to care.

Notwithstanding these challenges, there remains grounds for optimism. Each preterm infant represents a distinct potential for resilience and developmental success. By integrating advances in neuroscience, genetics, and personalised medicine, there lies the opportunity to unravel the complexities of this ‘BLACK BOX’, informing more effective, individualised therapeutic strategies. On this World Prematurity Day, we reaffirm our commitment to interdisciplinary research, innovation, and compassionate care to ensure every child born prematurely receives the best possible chance to achieve their cognitive and psychosocial potential.

Thanks to Ulrika Aden and Nelly Padilla for the feedback suggestions
Photo credit: Asha Judy Mary




References
1. Ådén, U., Farooqi, A., Hellstrom-Westas, L., Sävman, K., Abrahamsson, T., Björklund, L. J., ... & Norman, M. (2025). Long-term neurodevelopmental outcomes in extremely preterm infants born at 22–26 weeks gestation: a follow-up of 2–2.5 years across two Swedish national cohorts from 2004–2007 to 2014–2016. Archives of Disease in Childhood-Fetal and Neonatal Edition.
2. Nivins, S., Padilla, N., Kvanta, H., & Ådén, U. (2025). Gestational Age and Cognitive Development in Childhood. JAMA Network Open, 8(4), e254580-e254580.
3. Nivins, S., Padilla, N., Kvanta, H., Mårtensson, G., & Ådén, U. (2025). Distinct neural mechanisms underlying cognitive difficulties in preterm children born at different stages of prematurity. NeuroImage: Clinical, 103876.
4. Thalhammer, M., Seidlitz, J., Neubauer, A., Menegaux, A., Schmitz-Koep, B., Di Biase, M. A., ... & Sorg, C. (2025). Heterogeneous, temporally consistent, and plastic brain development after preterm birth. Nature Communications, 16(1), 8269.
Location: Sweden

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