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Early cortical maturation predicts neurodevelopment in very preterm infants
  1. Julia E Kline1,
  2. Venkata Sita Priyanka Illapani1,
  3. Lili He1,2,
  4. Mekibib Altaye2,3,
  5. John Wells Logan4,
  6. Nehal A Parikh1,2
  1. 1 Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
  2. 2 Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
  3. 3 Division of Biostatistics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
  4. 4 Department of Pediatrics, Nationwide Children's Hospital, Columbus, Ohio, USA
  1. Correspondence to Dr Nehal A Parikh, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; nehal.parikh{at}


Objective To evaluate the ability of four objectively defined, cortical maturation features—surface area, gyrification index, sulcal depth and curvature—from structural MRI at term-equivalent age (TEA) to independently predict cognitive and language development at 2 years corrected age in very preterm (VPT) infants.

Design Population-based, prospective cohort study. Structural brain MRI was performed at term, between 40 and 44 weeks postmenstrual age and processed using the developing Human Connectome Project pipeline.

Setting Multicentre study comprising four regional level III neonatal intensive care units in the Columbus, Ohio region.

Patients 110 VPT infants (gestational age (GA) ≤ 31 weeks).

Main outcome measures Cognitive and language scores at 2 years corrected age on the Bayley Scales of Infant and Toddler Development, Third Edition.

Results Of the 94 VPT infants with high-quality T2-weighted MRI scans, 75 infants (80%) returned for Bayley-III testing. Cortical surface area was positively correlated with cognitive and language scores in nearly every brain region. Curvature of the inner cortex was negatively correlated with Bayley scores in the frontal, parietal and temporal lobes. In multivariable regression models, adjusting for GA, sex, socioeconomic status, and injury score on MRI, regional measures of surface area and curvature independently explained more than one-third of the variance in cognitive and language scores at 2 years corrected age in our cohort.

Conclusions We identified increased cortical curvature at TEA as a new prognostic biomarker of adverse neurodevelopment in very premature infants. When combined with cortical surface area, it enhanced prediction of cognitive and language development. Larger studies are needed to externally validate our findings.

  • neonatology
  • neurodisability
  • neurodevelopment
  • neurology
  • outcomes research

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  • Contributors NP, LH, MA and JWL designed this study. NP, LH and JWL collected the data. JK, MA, VSPI and NP analysed the data. JK wrote the manuscript. JK, VSPI, LH, MA, JWL and NAP reviewed and edited the manuscript. All authors contributed to the interpretation of the data, the drafting and revision of this manuscript and the final approval of the version published. All authors agree to be accountable for all aspects of the work.

  • Funding This work was supported by National Institutes of Health grants R01-NS094200 and R01-NS096037.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request.

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