The literature on brain imaging in premature infants is mostly made up of studies that evaluate neonates, yet the most dynamic time of brain development happens from birth to 1 year of age. This study was designed to obtain quantitative brain measures from magnetic resonance imaging scans of infants born prematurely at 12 months of age.


The subject group was designed to capture a wide range of gestational age (GA) from premature to full-term infants. An age-specific atlas generated quantitative brain measures. A regression model was used to predict effects of GA and sex on brain measures.


There was a primary effect of sex on: (1) intracranial volume, males > females; (2) proportional cerebral cortical gray matter (females > males), and (3) cerebral white matter (males > females). GA predicted cerebral volume and cerebral spinal fluid. GA also predicted cortical gray matter in a sex-specific manner with GA having a significant effect on cortical volume in the males, but not in females.

Conclusions and relevance

Sex differences in brain structure are large early in life. GA had sex-specific effects highlighting the importance evaluating sex effects in neurodevelopmental outcomes of premature infants.

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We would like to thank all of the families who participated in our study. In addition, we acknowledge Corinne Hamlin, research coordinator for her time and effort. This study was supported by NIH grant 2P01 HL046925, National Institute for Heart, Lung and Blood (NHLBI). Preterm Transfusions: Brain Structure and Function Outcomes. The current study was funded by 2P01 HL046925 (Widness, PI), National Institutes of Heart, Lung and Blood and 1 U54 TR001013 (Rosenthal, PI), and NCATS which funds our Clinical Research Unit.

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Author notes

  1. These authors contributed equally: Amanda Benavides, Andrew Metzger


  1. Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, IA, 52242, USA

    • Amanda Benavides
    • , Alexander Tereshchenko
    •  & Peg Nopoulos
  2. Department of Radiology, Carver College of Medicine, University of Iowa, Iowa City, IA, 52242, USA

    • Andrew Metzger
    •  & Vince Magnotta
  3. Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA, 52242, USA

    • Amy Conrad
    • , Edward F. Bell
    •  & Peg Nopoulos
  4. School of Psychology, University of East Anglia, Norwich, England

    • John Spencer
  5. Department of Psychology, University of Tennessee, Knoxville, TN, 37996, USA

    • Shannon Ross-Sheehy
  6. Department of Pediatrics, School of Medicine, University of Minnesota, Minneapolis, MN, 55455, USA

    • Michael Georgieff
  7. Department of Neurology, Carver College of Medicine, University of Iowa, Iowa City, IA, 52242, USA

    • Peg Nopoulos


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Correspondence to Peg Nopoulos.

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