Increased Brain Age Gap Estimate (BrainAGE) in Young Adults After Premature Birth

Dennis M. Hedderich, Aurore Menegaux, Benita Schmitz-Koep, Rachel Nuttall, Juliana Zimmermann, Sebastian C. Schneider, Josef G. Bäuml, Marcel Daamen, Henning Boecker, Marko Wilke, Claus Zimmer, Dieter Wolke, Peter Bartmann, Christian Sorg, Christian Gaser

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Recent evidence suggests increased metabolic and physiologic aging rates in premature-born adults. While the lasting consequences of premature birth on human brain development are known, its impact on brain aging remains unclear. We addressed the question of whether premature birth impacts brain age gap estimates (BrainAGE) using an accurate and robust machine-learning framework based on structural MRI in a large cohort of young premature-born adults (n = 101) and full-term (FT) controls (n = 111). Study participants are part of a geographically defined population study of premature-born individuals, which have been followed longitudinally from birth until young adulthood. We investigated the association between BrainAGE scores and perinatal variables as well as with outcomes of physical (total intracranial volume, TIV) and cognitive development (full-scale IQ, FS-IQ). We found increased BrainAGE in premature-born adults [median (interquartile range) = 1.4 (−1.3–4.7 years)] compared to full-term controls (p = 0.002, Cohen’s d = 0.443), which was associated with low Gestational age (GA), low birth weight (BW), and increased neonatal treatment intensity but not with TIV or FS-IQ. In conclusion, results demonstrate elevated BrainAGE in premature-born adults, suggesting an increased risk for accelerated brain aging in human prematurity.

Original languageEnglish
Article number653365
JournalFrontiers in Aging Neuroscience
StatePublished - 1 Apr 2021
Externally publishedYes


  • aging
  • brain
  • development
  • magnetic resonance imaging
  • premature birth


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