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

Journal of Perinatology volume 41, pages 519–527 (2021)Cite this article

Subjects

Abstract

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.

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Fig. 1: Mediation analysis.

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Acknowledgements

The authors would like to express our gratitude to the families who participated in the study and the clinical and administrative staff in the High-risk Follow-up Clinic at Nationwide Children’s Hospital

Funding

This study was supported, in part, by the National Institute of Neurological Disorders and Stroke, United States (NIH Grants R01-NS094200 and R01-096037).

Author information

Authors and Affiliations

  1. Department of Pediatrics, Nationwide Children’s Hospital, The Ohio State University, Columbus, OH, USA

    J. W. Logan, O. Fathi & M. Klebanoff

  2. Biostatistics Resource at Nationwide Children’s Hospital, Nationwide Children’s Hospital, Columbus, OH, USA

    J. Tan

  3. Cincinnati Children’s Hospital Medical Center, Perinatal Institute, Cincinnati, OH, USA

    M. Skalak, L. He, J. Kline & N. A. Parikh

  4. Center for Perinatal Research, The Research Institute at Nationwide Children’s Hospital, The Ohio State University, Columbus, OH, USA

    M. Klebanoff

  5. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA

    N. A. Parikh

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  1. J. W. Logan
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Contributions

JWL wrote the manuscript. JWL and NAP conceived and designed the study, performed intermediate analyses, and reviewed statistical findings. MK reviewed statistical methods, participated in intermediate analyses, and reviewed the manuscript. JT performed statistical analyses. NAP, JK and LH participated in MRI analytics that resulted in formation of the dataset. MS conducted analyses related to the global injury score, including validation metrics. JWL, NAP, MK, OF, JK, MS, and LH reviewed the manuscript and approved the final draft.

Corresponding author

Correspondence to J. W. Logan.

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The authors declare that they have no conflict of interest.

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Logan, J.W., Tan, J., Skalak, M. et al. Adverse effects of perinatal illness severity on neurodevelopment are partially mediated by early brain abnormalities in infants born very preterm. J Perinatol 41, 519–527 (2021). https://doi.org/10.1038/s41372-020-00854-1

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