Increasing prematurity is associated with a more pronounced delay in brain maturation in older children and adolescents

Aims: Prematurity is a substantial risk factor for an unfavorable neurodevelopmental outcome, particularly for babies born ≤32 weeks of gestation. We here aimed to assess whether a delay in brain maturation is still detectable in former preterms in late childhood and adolescence, as a function of their prematurity.

Methods: Overall, 70 children (7 to 17 years old, mean age = 13.07; 38 males) were included; 39 were healthy, term-born controls, and 31 were preterm-born (23.9 to 32 weeks). MRI data were acquired on a Siemens Avanto 1.5T MR scanner and preprocessed using SPM8, VBM8, and MATLAB. We used the BrainAGE framework to assess high-resolution T1-weighted MR datasets; this approach applies the pattern of normal development to an individual's dataset and yields an estimated age (in years). The estimated age is then related to the true age of the subject, with a value of < 0 indicating a delay in maturation. For training the algorithm, MR data from an additional 394 children were used, acquired as part of the NIH study of normal brain development.¹

Results: Term children's ages were accurately estimated. Estimated age and true age are highly correlated, calculated using gray matter (GM, r = 0.85, p < 0.001) or white matter volumes (WM, r = 0.83, p < 0.001), with a mean absolute error 1.16 and 1.32 years, respectively. Preterm children's gestational age is significantly correlated with their BrainAGE score calculated using GM and WM volumes (r = 0.50, p < 0.005), indicating that our approach sensitively detects a significantly larger maturational delay (up to 2 years) in children and adolescents born more preterm.

Conclusion: We were able to confirm the ability of the BrainAGE framework to accurately determine the age of healthy children,² with a margin of error of only ˜1.2 years. When applied to a large cohort of older children and adolescents formerly born very preterm, a significant delay in brain maturation was found, which was significantly correlated with increasing prematurity. This study provides further evidence for long-term neurobiological consequences of premature birth.

References

1. Evans AC; Brain Development Cooperative Group. The NIH MRI study of normal brain development. Neuroimage 2006;30(1):184 – 202

2. Franke K, Luders E, May A, Wilke M, Gaser C. Brain maturation: predicting individual BrainAGE in children and adolescents using structural MRI. Neuroimage 2012;63(3):1305 – 1312