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Usefulness of serum neurofilament light in the assessment of neurologic outcome in the pediatric population: a systematic literature review

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Abstract

Children undergoing general anesthesia and surgery in the early years of life are exposed to the possible neurotoxicity of anesthetic agents. Prospective studies have shown deficits in behavior, executive function, social communication, and motor function in children undergoing anesthesia and surgery. Different biomarkers of neuronal injury have been evaluated neuronal injury in the pediatric population, among which neurofilaments represent a significant advantage as they are proteins exclusively expressed in neuronal tissue. Our aim was to evaluate the utility of serum neurofilament light (NfL) as a prognostic biomarker of neuronal injury in the pediatric population. A literature search was performed on PubMed, Embase, and Cochrane Databases in November 2022 for studies concerning serum NfL in the pediatric population in addition to a neurological assessment. Inclusion criteria were as follows: (1) prospective or retrospective studies, (2) studies including pediatric population until the age of 18 years, (3) serum NfL sampling, and (4) evaluation of neurological outcome. Data collection regarding study design, pediatric age, serum NfL levels, and results for neurological assessment were extracted from each study. Four manuscripts met the inclusion criteria and evaluated the prognostic utility of serum NfL in neonatal encephalopathy in correlation with the neurodevelopmental outcome that was assessed by the Bayley Scales of Infant Development until the age of 2 years. Children with neonatal encephalopathy showed significantly higher serum NfL vs. healthy controls and high serum NfL levels predicted an adverse neurological outcome. The decrease of serum NfL to a nadir point between 10 and 15 years old reflects the brain growth in healthy controls. No studies were available in the perioperative period.

  Conclusions: Serum NfL is a valuable biomarker in evaluating neuronal injury in the pediatric population. Further studies with perioperative serial sampling of serum NfL combined with standardized neurodevelopmental tests should be conducted to evaluate the neurotoxicity of anesthetic agents and monitor the effectiveness of specific neuroprotective strategies in pediatric patients undergoing anesthesia and surgery.

What is Known:

• Preclinical animal data have shown neurotoxicity of the anesthetic agents in the developing brain.

• Data regarding anesthetic neurotoxicity in humans show limitations and no objective tools are available.

What is New:

• This systematic review showed that serum NfL is a valuable biomarker of neuronal injury in the pediatric population.

• Perioperative use of serum NfL may be considered in future trials evaluating anesthetic neurotoxicity in the pediatric population and in monitoring neuroprotective strategies.

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Fig. 1

Data availability

All data generated or analysed during this study are included in this published article.

Abbreviations

GABA:

Gamma-aminobutyric acid

NMDA:

N-Methyl-D-Aspartate

NfL:

Neurofilament light

TH:

Therapeutic hypothermia

HIE:

Hypoxic-ischemic encephalopathy

IQR:

Interquartile range

BSID:

Bayley Scales of Infant Development

GFAP:

Glial fibrillary acidic protein

UCH-L1:

Ubiquitin C-terminal hydrolase-L1

Simoa:

Single-molecule array

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Contributions

Independent literature search, extraction of data, and interpretation of data were performed by Aurélie Jacobs Sariyar (AJS) and Mona Momeni (MM). The first draft of the manuscript was written by Aurélie Jacobs Sariyar (AJS) and Mona Momeni (MM). All authors critically reviewed the manuscript for intellectual content and commented on the previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Aurélie Jacobs Sariyar.

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Jacobs Sariyar, A., van Pesch, V., Nassogne, MC. et al. Usefulness of serum neurofilament light in the assessment of neurologic outcome in the pediatric population: a systematic literature review. Eur J Pediatr 182, 1941–1948 (2023). https://doi.org/10.1007/s00431-022-04793-1

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