Abstract
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.
Highlights
Premature birth, i.e., birth before 37 weeks of gestation, has a worldwide prevalence of around 11% (Chawanpaiboon et al, 2019)
We investigate the impact of premature birth on biological brain age in young adulthood in a large cohort of individuals born very preterm and/or at very low birth-weight (VP/very low birth weight (VLBW)) and age-matched controls born at full-term (FT), who were followed from birth until adulthood in a longitudinal, population-based cohort study
Of the initial 916 full-term born infants from the same obstetric hospitals that were alive at 6 years, 350 were randomly selected as control subjects within the stratification variables of sex and family socioeconomic status to be comparable with the VP/VLBW sample
Summary
I.e., birth before 37 weeks of gestation, has a worldwide prevalence of around 11% (Chawanpaiboon et al, 2019). Due to the increasingly recognized importance of early and mid-adulthood as a window for interventions aiming at the prevention of age-related brain disorders such as Alzheimer’s disease, the need for a valid biomarker of brain aging over the life span was emphasized (Belsky et al, 2015; Elliott et al, 2019) One such concept relies on the fact that some people experience faster biological degradation than others, resulting in an offset between ‘‘biological’’ and ‘‘chronological’’ age (Belsky et al, 2015; Elliott, 2020). We hypothesized that these alterations in BrainAGE are distinct from established markers of physical and cognitive developmental outcomes
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