Elevated Blood NfL a Marker for Poor Pediatric Cardiac Arrest Outcomes

GFAP, UCH-L1, NfL, and tau biomarker concentrations are higher in children with an unfavorable vs favorable outcome at 1 year following pediatric cardiac arrest.

Elevated neurofilament light (NfL) may be a marker for poor clinical outcomes following pediatric cardiac arrest, according to a multicenter prospective cohort study published in JAMA Network Open.

Cardiac arrest occurs among approximately 10,000 children every year in the United States. Some children experience return of spontaneous circulation which is associated with neurological morbidity and death. To date, no risk assessment tools for determining neurological damage risk have been developed.

The Personalizing Outcomes After Child Cardiac Arrest (POCCA) study was conducted at 14 sites in the US between 2017 and 2020. Children (N=120) admitted to the intensive care unit for cardiac arrest were evaluated for blood-based brain injury markers. Potential biomarkers were compared with outcomes at 1 year. Unfavorable outcomes were defined as death or Vineland Adaptive Behavior Scales (VABS-3) score of <70.

The study population comprised 59.2% boys aged median 1.0 (interquartile range [IQR], 0-8.5) years, 67.2% were White, and 68.1% had preexisting conditions.

At 1 year, 70 had favorable outcomes and 50 unfavorable outcomes of death (n=43) or low VABS-3 scores (n=7).

In this cohort study, blood-based brain injury biomarkers, especially NfL, were associated with an unfavorable outcome at 1 year after pediatric cardiac arrest.

The unfavorable group had a higher rate of out of hospital cardiac arrest (70.0% vs 35.7%; P <.001), longer duration of cardiopulmonary resuscitation (median, 20.0 vs 5.0 min; P <.001), fewer of events were witnessed (54.0% vs 92.9%; P <.001), more had bystander resuscitation (50.0% vs 24.3%; P =.004), and they received more doses of epinephrine (median, 2.5 vs 1.0; P =.04) compared with individuals in the favorable cohort, respectively.

Individuals in the unfavorable cohort had elevated biomarkers on days 1, 2, and 3 compared with the favorable group. For example, on day 1, among individuals in the unfavorable and favorable cohorts, these were the biomarker concentrations, respectively:

  • Median NfL concentrations were 50.54 and 13.81 pg/mL (P <.001)
  • Ubiquitin carboxyl-terminal esterase L1 (UCH-L1) levels were 310.40 and 73.39 pg/mL (P <.001)
  • Tau levels were 50.10 and 5.59 pg/mL (P <.001)

Glial fibrillary acidic protein (GFAP) levels were 469.88 and 174.85 pg/mL (P =.002).

For predicting 1-year outcomes, tau at day 1 (area under the receiver operating characteristic curve [AUROC], 0.333; 95% CI, 0.204-0.484) and UCH-1 at days 2 (AUROC, 0.581; 95% CI, 0.421-0.730) and 3 (AUROC, 0.605; 95% CI, 0.434-0.760) were the most accurate predictors.

Unfavorable outcomes were associated with:

 aOR (95%, CI)
BiomarkerDay 1Day 2Day 3
    NfL5.91 (1.82-19.19)11.88 (3.82-36.92)10.22 (3.14-33.33)
    UCH-L12.01 (0.84-4.84)11.27 (3.00-42.36)7.56 (2.11-27.09)
    GFAP1.36 (0.72-2.59)2.31 (1.19-4.48)2.19 (1.19-4.03_
    Tau2.44 (1.14-5.25)2.28 (1.31-3.97)2.04 (1.16-3.57)

Covariates frequently associated with poor outcomes included unwitnessed events, Pediatric Index of Mortality 3 score, and lack of targeted temperature management for hypothermia.

The major limitation of this study was that 28.3% of potentially eligible children had no blood sample within the first 24 hours and were removed from this analysis.

During the first 3 days following pediatric cardiac arrest, especially NfL on days 2 and 3, NfL, were strong predictors for 1-year outcomes.

“In this cohort study, blood-based brain injury biomarkers, especially NfL, were associated with an unfavorable outcome at 1 year after pediatric cardiac arrest,” the researchers concluded.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Fink EL, Kochanek PM, Panigrahy A, et al. Association of blood-based brain injury biomarker concentrations with outcomes after pediatric cardiac arrest. JAMA Netw Open. 2022;5(9):e2230518. doi:10.1001/jamanetworkopen.2022.30518