Establishment of normal reference values of NT-proBNP and its application in diagnosing acute heart failure in children with severe hand food and mouth disease

Abstract

Hand, foot, and mouth disease (HFMD), caused by enteroviruses, is an acute contagious disease in children. Some severe infections caused by human enterovirus 71 (HEV71) lead to rapid death in children with acute heart failure (HF). N-terminal probrain natriuretic peptide (NT-proBNP) is an important indicator of HF; however, its normal reference values in children and role in HFMD remain unclear.This study aimed to investigate the correlation between NT-proBNP and heart function and establish normal reference values of NT-proBNP in children with HFMD aged 0 to 18 years.In this study, 95% normal reference values were established in 1031 healthy children aged 0 to 18 years. The correlation between NT-proBNP and left ventricular ejection (LVEF) was analyzed in 392 children with HFMD using Spearman correlation and receiver operating characteristic analysis.NT-proBNP levels were negatively correlated with LVEF in 392 children with HFMD. The median NT-proBNP level was 921 pg/mL in the early cardiorespiratory failure group, but only 55 pg/mL in the nervous system involvement group. Serum NT-proBNP levels were negatively correlated with age. The normal reference value in the neonatal period (0 to <1 month) and adolescence (13–18 years) was 250.0 to 3987.0 pg/mL and 20.0 to 145.0 pg/mL, respectively.NT-proBNP levels can reflect the severity of HFMD and discriminate the second stage from the third stage of HFMD effectively. NT-proBNP is a useful biomarker to predict the early stage of severe HFMD in children with HF. Different ages fit with different normal reference values of NT-proBNP in children.

NT-proBNP Concentrations in the Umbilical Cord and Serum of Term Neonates: A Systematic Review and Meta-Analysis

“…The studies that compose the present review are depicted in Table 2 [ 21 , 26 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 ].…”

“…Another observation is that NT-proBNP levels gradually decrease as the ages of the neonate’s advance. Several studies have reported a negative correlation between NT-proBNP values and age such as the studies of Rauh et al [ 41 ] (r = −0.45, p < 0.001), Li et al [ 46 ] (r = −0.23, p < 0.05), and Deng et al [ 48 ] (r = −0.706, p = 0.000). Nir et al [ 42 ] reported significantly higher levels of the biomarker during the neonate’s first days of life as opposed to later days ( p < 0.05), while infants between 4 months and 15 years old did not exhibit a remarkably wide range of values (regression analysis, r 2 = 0.18).…”

“…The decrease in plasma NT-proBNP can be attributed to the diuresis that goes along with renal maturation, the suppression of renin-aldosterone-angiotensin I and II system activity, and the neonate’s water loss increase postnatally [ 68 ]. The gradual serum level decrease in the biomarker continues until the first months of life and remains considerably stable from infancy to the beginning of adolescence [ 25 , 26 , 41 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 52 , 54 , 69 ].…”

Astragaloside IV alleviates myocardial damage induced by type 2 diabetes via improving energy metabolism

“…CNP is involved in the regulation of myocardial changes in myocardial infarction, ischemia-reperfusion and heart failure, but its expression level was also affected by blood pressure and vascular endothelial cells, which cannot specifically respond to myocardial changes. Although NT-proBNP has no biological activity, it has a longer half-life and is more stable than BNP, and has been proposed as a biomarker of heart failure by the American Society of Clinical Chemistry (40–42). However, NT-proBNP could not reflect the changes in cardiac myocytes.…”

Establishment and Verification of Sex- and Age-Specific Serum Electrolyte Reference Intervals in Healthy Han Children in Changchun, Northeastern China

“…For instance, serum electrolytes and liver function tests of Han Chinese healthy adult population were found to be different from those of children's [4, 11]. One study found the reference intervals of N -terminal probrain natriuretic peptide (NT-proBNP) in the neonatal period (0 to <1 month) and adolescence (13–18 years) were quite different (250.0 to 3987.0 pg/ml vs 20.0 to 145.0 pg/ml) [12]. Age-related differences in reference intervals of children were statistically significant for Ca, Fe, Cu, Mg, and Zn [13].…”