Establishment of normal reference values of NT-proBNP and its application in diagnosing acute heart failure in children with severe hand foot and mouth disease [corrected].

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.