A Pilot Study of Soluble Form of LOX-1 as a Novel Biomarker for Neonatal Hypoxic-Ischemic Encephalopathy

J Pediatr. 2019 Mar:206:49-55.e3. doi: 10.1016/j.jpeds.2018.10.036. Epub 2018 Dec 12.

Abstract

Objective: To evaluate the soluble form of lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) as a biomarker of severity staging and prognosis in neonatal hypoxic-ischemic encephalopathy (HIE).

Study design: We performed an observational study enrolling 27 infants with HIE and 45 control infants of gestational age ≥36 weeks and birth weight ≥1800 g. The HIE criteria were pH ≤7.0 or a base deficit ≥16 mmol/L within 60 minutes after birth, and a 10-minute Apgar score ≤5 or resuscitation time ≥10 minutes. HIE severity was evaluated using modified Sarnat staging. We measured plasma sLOX-1 level and assessed general and neurologic signs at discharge, and classified infants with no neurosensory impairments as intact survival.

Results: sLOX-1 level within 6 hours after birth was correlated with the severity of HIE. sLOX-1 differentiated moderate-severe HIE (median, 1017 pg/mL; IQR, 553-1890 pg/mL) from mild HIE (median, 339 pg/mL; IQR, 288-595 pg/mL; P = .007). The sensitivity and specificity of the differentiation with a cutoff value of ≥550 pg/mL were 80.0% and 83.3%, respectively. In 19 infants with therapeutic hypothermia, a sLOX-1 cutoff value of <1000 pg/mL differentiated intact survival (median, 761 pg/mL; IQR, 533-1610 pg/mL) from death or neurosensory impairment (median, 1947 pg/mL; IQR, 1325-2506 pg/mL; P = .019) with 100% specificity and a positive predictive value.

Conclusion: sLOX-1 may be a useful biomarker of neonatal HIE for severity staging and outcome prediction. Further investigations will facilitate its clinical use.

Keywords: biomarker; clinical observation; hypothermia.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / blood*
  • Female
  • Humans
  • Hydrogen-Ion Concentration
  • Hypothermia, Induced
  • Hypoxia-Ischemia, Brain / blood*
  • Hypoxia-Ischemia, Brain / diagnosis*
  • Infant, Newborn
  • Male
  • Pilot Projects
  • Predictive Value of Tests
  • Prognosis
  • Prospective Studies
  • Scavenger Receptors, Class E / blood*
  • Sensitivity and Specificity
  • Severity of Illness Index

Substances

  • Biomarkers
  • OLR1 protein, human
  • Scavenger Receptors, Class E