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The long-term effect of erythropoiesis stimulating agents given to preterm infants: a proton magnetic resonance spectroscopy study on neurometabolites in early childhood

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Abstract

Background

Erythropoiesis stimulating agents (ESAs) are neuroprotective in cell and animal models of preterm birth. Prematurity has been shown to alter neurometabolite levels in children in studies using proton magnetic resonance spectroscopy (1H-MRS).

Objective

We hypothesized that ESA treatment in premature infants would tend to normalize neurometabolites by 4–6 years of age.

Materials and methods

Children in a longitudinal study of neurodevelopment underwent MRI and 1H-MRS at approximately 4 years and 6 years of age. Prematurely born children (500–1,250 g birth weight) received ESAs (erythropoietin or darbepoetin) or placebo during their neonatal hospitalization, and these groups were compared to healthy term controls. 1H-MRS spectra were obtained from the anterior cingulate (gray matter) and frontal lobe white matter, assessing combined N-acetylaspartate and N-acetylaspartylglutamate (tNAA), myo-inositol, choline compounds (Cho), combined creatine and phosphocreatine, and combined glutamate and glutamine.

Results

No significant (P≤0.5) group differences were observed for any metabolite level. Significant age-related increases in white-matter tNAA and Cho were observed, as well as a trend for increased gray-matter tNAA.

Conclusion

Neither prematurity nor neonatal ESA treatment was associated with differences in brain metabolite levels in the children of this study at a significance level of 0.05. These findings suggest that earlier differences that might have existed had normalized by 4–6 years of age or were too small to be statistically significant in the current sample.

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Acknowledgments

This work was supported by grants from the National Institutes of Health NICHD (R01-HD059856), the Thrasher Research Fund, and the University of New Mexico Clinical and Translational Science Center (UL1 TR001449).

The authors wish to thank research coordinators and bedside nurses involved in the original randomized study. We also wish to thank Sarah Peceny and Sean Gonzales for subject coordination, Cathy Smith and Diana South for performing the scans, Joy Van Meter and the subject monitors who assisted during late night scanning. We are also indebted to the parents of our subjects who allow their children to participate in this study and provide inspiration and motivation for this work. Finally, we need to acknowledge all U.S. taxpayers, who provide funding to support the National Institutes of Health and this study.

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Authors and Affiliations

  1. Mind Research Network, University of New Mexico Health Sciences Center, Albuquerque, NM, USA

    Charles Gasparovic, Arvind Caprihan & John Phillips

  2. Department of Psychology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA

    Ronald A. Yeo

  3. Department of Neurology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA

    John Phillips

  4. Department of Pediatrics, MSC10 5590, 1 University of New Mexico, Albuquerque, NM, 87131-0001, USA

    Jean R. Lowe & Robin K. Ohls

  5. Psychiatry and Behavioral Sciences, University of New Mexico Health Sciences Center, Albuquerque, NM, USA

    Richard Campbell

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  1. Charles Gasparovic
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  2. Arvind Caprihan
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  4. John Phillips
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  7. Robin K. Ohls
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Correspondence to Robin K. Ohls.

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Gasparovic, C., Caprihan, A., Yeo, R.A. et al. The long-term effect of erythropoiesis stimulating agents given to preterm infants: a proton magnetic resonance spectroscopy study on neurometabolites in early childhood. Pediatr Radiol 48, 374–382 (2018). https://doi.org/10.1007/s00247-017-4052-1

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  • DOI: https://doi.org/10.1007/s00247-017-4052-1

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