Pediatric Cardiology

, Volume 40, Issue 3, pp 546–553 | Cite as

A Novel Brain Injury Biomarker Correlates with Cyanosis in Infants with Congenital Heart Disease

  • Lindsey McPhillipsEmail author
  • Dipak Kholwadwala
  • Cristina P. Sison
  • Dorota Gruber
  • Kaie OjamaaEmail author
Original Article


Cyanotic heart lesions are a complex subset of congenital heart disease (CHD) in which patients are desaturated until surgical repair or palliation. We hypothesized that a direct relationship would exist between degree of desaturation and presence of systemic inflammation and brain injury in unrepaired patients less than 1 year of age. The pre-operative desaturation with augmented systemic inflammation would predict a more complex post-operative course. Fifty patients with CHD were enrolled in this study and classified as cyanotic (O2 ≤ 90%) or acyanotic (O2 > 90%) based on SpO2. Serum inflammatory mediators measured included interleukins (IL)-6, IL-8, IL-12p70, IL-10, IL-1β, tumor necrosis factor (TNF)-α, interferon (INF)-γ; macrophage inhibitory factor (MIF) and a novel brain biomarker, phosphorylated neurofilament heavy subunit (pNF-H). Twenty-two cyanotic and 28 acyanotic subjects were enrolled with SpO2 of 78 ± 18% and 98 ± 2% (p < 0.001), respectively, and mean age of 72 days (range 2–303) and 102 days (range 1–274), respectively. Cyanotic vs acyanotic subjects had elevated serum IL-6 (6.6 ± 7.6 vs 2.9 ± 2.9 pg/ml, p = 0.019) and pNF-H (222 ± 637 vs 57 ± 121 pg/ml, p = 0.046), and both biomarkers correlated with degree of desaturation (Spearman rank-order correlation ρ = − 0.30, p = 0.037 and ρ = − 0.29 p = 0.049, respectively). Post-operative inotrope scores at 24 h and duration of mechanical ventilation correlated inversely with pre-operative oxygen saturation (ρ = − 0.380, p = 0.014 and ρ = − 0.362, p = 0.020, respectively). The degree of pre-operative desaturation correlated with a more complicated post-operative course supporting the need for advanced peri-operative therapy in this population.


Congenital heart disease Systemic inflammation Brain injury Cytokines Neurofilament Bypass surgery 



This study was not funded.

Compliance with Ethical Standards

Conflict of interest

None of the authors have any conflict of interest.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed Consent

Informed consent was obtained from all individual participants included in the study.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of Pediatric Cardiology, Department of PediatricsCohen Children’s Medical Center of New York at Northwell HealthNew Hyde ParkUSA
  2. 2.Barbara and Donald Zucker School of Medicine at Hofstra/NorthwellHempsteadUSA
  3. 3.Biostatistics UnitThe Feinstein Institute for Medical Research, Northwell HealthManhassetUSA
  4. 4.Department of Biomedical SciencesNew York Institute of Technology College of Osteopathic MedicineOld WestburyUSA

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