Growth of prefrontal and limbic brain regions and anxiety disorders in children born very preterm

Background Children born very preterm (VP) display altered growth in corticolimbic structures compared with full-Term peers. Given the association between the cortiocolimbic system and anxiety, this study aimed to compare developmental trajectories of corticolimbic regions in VP children with and without anxiety diagnosis at 13 years. Methods MRI data from 124 VP children were used to calculate whole brain and corticolimbic region volumes at term-equivalent age (TEA), 7 and 13 years. The presence of an anxiety disorder was assessed at 13 years using a structured clinical interview. Results VP children who met criteria for an anxiety disorder at 13 years (n = 16) displayed altered trajectories for intracranial volume (ICV, p < 0.0001), total brain volume (TBV, p = 0.029), the right amygdala (p = 0.0009) and left hippocampus (p = 0.029) compared with VP children without anxiety (n = 108), with trends in the right hippocampus (p = 0.062) and left medial orbitofrontal cortex (p = 0.079). Altered trajectories predominantly reflected slower growth in early childhood (0-7 years) for ICV (β =-0.461, p = 0.020), TBV (β =-0.503, p = 0.021), left (β =-0.518, p = 0.020) and right hippocampi (β =-0.469, p = 0.020) and left medial orbitofrontal cortex (β =-0.761, p = 0.020) and did not persist after adjusting for TBV and social risk. Conclusions Region-and time-specific alterations in the development of the corticolimbic system in children born VP may help to explain an increase in anxiety disorders observed in this population.