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  • Clinical Research Article
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Early motor outcomes in infants with complex congenital heart disease: the predictive role of NSE and S100B

Pediatric Research (2025)Cite this article

Abstract

Background

Children with complex congenital heart disease (CCHD) are at high risk for early neurodevelopmental delays across all domains. Neuromotor delay often emerges first and may impact broader development. Identifying early biomarkers of motor function could capture a critical window for intervention. We assessed the prognostic value of neuron-specific enolase (NSE) and S100B in predicting 4-month motor outcomes in newborns undergoing cardiac surgery with cardiopulmonary bypass (CPB).

Methods

Between December 2021 and October 2024, we conducted a prospective, single-centre study including term neonates with (CCHD) who required cardiac surgery within the first two months of life. NSE and S100B levels were measured at five perioperative time points. Blinded Alberta Infant Motor Scale (AIMS) assessment at four months evaluated motor outcomes.

Results

Of 35 newborns, 27 completed follow-up. Preoperative NSE levels were significantly higher in infants with AIMS scores below the 10th percentile (32.7 vs. 20.9 ng/mL, p = 0.044) and negatively correlated with AIMS percentiles (ρ = –0.617, p = 0.006. There was no significant association between motor outcomes, MRI findings or S100B levels.

Conclusions

Higher preoperative NSE levels predict poor early motor outcomes in CCHD and may be a marker for early risk stratification and intervention.

Impact

  • Neuron-specific enolase (NSE) may serve as an early biomarker of neuromotor development in newborns with complex congenital heart disease (CCHD). Elevated preoperative NSE levels were associated with poorer motor outcomes at four months. NSE may serve as an additional biomarker within a multimodal risk stratification strategy, complementing clinical, imaging, and electrophysiological assessments to refine prognostic evaluation. These findings highlight the prognostic value of perioperative biomarkers for predicting early motor outcomes and support earlier identification of at-risk newborns, enabling targeted neurodevelopmental interventions. This work adds new evidence to limited literature on biological predictors of motor development after neonatal cardiac surgery.

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Fig. 1: Four-month follow-up of newborns with CCHD operated on within the first two months of life.
Fig. 2: Evolution of NSE and S100B biomarkers over time in the total cohort and by AIMS groups.
Fig. 3: Spearman correlations between NSE and S100B levels and AIMS percentile scores.
Fig. 4: Correlation matrices between clinical variables, biomarkers, and motor outcome (AIMS percentile).

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Data availability

the datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We are grateful to all patients and their families who participated in this study. Disclosure of conflict of interest: None of the authors has any conflict of interest to disclose.

Funding

This study was supported by a Young Investigator Grant (AORC Jeune Chercheur) awarded by the GIRCI Méditerranée.

Author information

Author notes

  1. These authors contributed equally: Narjess Boutalbi, Samuel Dahan.

Authors and Affiliations

  1. Pediatric Neurology Department, Timone Enfant, APHM, Marseille, France

    Narjess Boutalbi, Thibault Beretti, Laurene Fortis, Lucie Delefosse, Robin Cloarec, Mathieu Milh & Béatrice Desnous

  2. Pediatric Anesthesia and Intensive Care Unit, APHM La Timone, Marseille, France

    Samuel Dahan, Stéphane Lebel, Solène Denantes, Matthieu Laborier, Sophie Arnaud, Dominique Santelli, Edouard Aries, Chloé Allary & Fabrice Michel

  3. Institut de Neurosciences des Systèmes, INSERM U1106, Marseille, France

    Samuel Dahan & Béatrice Desnous

  4. Neonatology Department, APHM La Conception, Marseille, France

    William Rozalen, Isabelle Grandvuillemin, Clotilde Desrobert & Farid Boubred

  5. Neuroradiology Department, APHM La Timone, Marseille, France

    Benoit Testud

  6. CEMEREM, APHM La Timone, Marseille, France

    Benoit Testud

  7. Division of Paediatric Cardiac Surgery, APHM La Timone, Marseille, France

    Virginie Fouilloux, Célia Gran & Marien Lenoir

  8. Aix Marseille University, CNRS, LPL, Aix-en-Provence, France

    Giulia Danielou

  9. Paediatric Cardiology Department, APHM La Timone, Marseille, France

    Florent Paoli, Fedoua El-Louali, Julie Blanc, Camille Velly, Guillaume Carles, Chloe Wanert, Sophie Quennelle, Edouard Aries & Caroline Ovaert

  10. Pediatric Anesthesia and Intensive Care Unit, Nantes, France

    Pierre Bourgoin

  11. French National Institute of Health and Medical Research, Inserm, U1046 PhyMedExp, Cardiac Neurodevelopmental Research Group, Montpellier, France

    Johanna Calderon

  12. Marseille Medical Gentics, Inserm UMR 125, Marseille, France

    Caroline Ovaert

  13. Aix Marseille University, INMED, Marseille, France

    Mathieu Milh

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  1. Narjess Boutalbi
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  2. Samuel Dahan
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  3. William Rozalen
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Contributions

B.D. conceived the study. TB, WR, LD, NB, and S.D collected and curated the data. NB and SD performed the statistical analyses. NB, SD and BD interpreted the results. B.D., ML, NB, SD drafted the manuscript with input from all authors. All authors critically revised the manuscript and approved the final version.

Corresponding author

Correspondence to Béatrice Desnous.

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Boutalbi, N., Dahan, S., Rozalen, W. et al. Early motor outcomes in infants with complex congenital heart disease: the predictive role of NSE and S100B. Pediatr Res (2025). https://doi.org/10.1038/s41390-025-04437-8

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