Adverse effects of perinatal illness severity on neurodevelopment are partially mediated by early brain abnormalities in infants born very preterm

J Perinatol. 2021 Mar;41(3):519-527. doi: 10.1038/s41372-020-00854-1. Epub 2020 Oct 7.


Background: We sought to determine the mediating effects of magnetic resonance imaging (MRI) biomarkers at term gestation on the relationship between perinatal illness severity and neurodevelopment.

Methods: The Clinical Risk Index for Babies-second edition (CRIB-II) was correlated with indices of brain maturation or injury and neurodevelopment at 2-year follow-up in infants born less than 32 weeks gestation. Using a counterfactual mediation analysis, associations between CRIB-II, MRI biomarkers, and neurodevelopment were confirmed, followed by an assessment of the mediating effects of MRI biomarkers on the relationship between CRIB-II and neurodevelopment.

Results: CRIB-II correlated significantly with neurodevelopment and MRI biomarkers of brain injury or cortical maturation. Two MRI biomarkers, cortical surface area and global injury score, were associated with neurodevelopmental scores at follow-up and included in mediation analyses.

Conclusion: Biomarkers of cortical maturation or brain injury at term-equivalent age mediated a substantial portion of the risks conveyed by perinatal illness severity on neurodevelopmental outcomes at 2 years corrected age.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Brain / diagnostic imaging
  • Child, Preschool
  • Gestational Age
  • Humans
  • Infant
  • Infant, Extremely Premature*
  • Infant, Newborn
  • Magnetic Resonance Imaging
  • Neurodevelopmental Disorders* / etiology