Reference range of plasma N-terminal pro-brain natriuretic peptide levels in early preterm infants

Objective To establish the reference range of plasma N-terminal pro-brain natriuretic peptide(NT-proBNP) levels in early preterm infants. Methods 1.Inclusion criteria of the subjects: (1) preterm infants admitted to Neonatal Ward of First Affiliated Hospital of Zhengzhou University between Oct.2009 and Aug.2012 within 24 hours after birth; (2) maternal health during pregnancy; (3) written informed consent obtained from parents; (4) normal laboratory examination results such as blood gas analysis, electrolyte, hepatorenal function, myocardial enzyme, routine blood count and infectious disease screening (hepatitis B, hepatitis C, syphilis and acquired immune deficiency syndrome) within 24 hours after birth.Plasma NT-proBNP levels were measured on day 1, day 3 and day 7 of life.Variable data was analyzed using the Shapiro-Wilk test for normality test.Difference in plasma NT-proBNP levels on different days of life was analyzed using repeated measure analysis of variance.A multiple regression analysis was performed to determine the influencing factors for plasma NT-proBNP level, reference value interval: reference range containing 95% of the reference population, namely(-1.96 s)-(+ 1.96 s), with inspection level α= 0.05. Results 1.A total of 204 preterm infants (104 cases were male and 100 cases were female) were included in the present study, with gestational age ranging from 27+ 1 to 36+ 6 weeks(median 33 weeks) and birth weight ranging from 700 to 3050 g (median 1590 g). Of these preterm infants, vaginal delivery were 78 cases, cesarean delivery in 126 cases, serum bilirubin level was (56.6±23.1)μmol/L, maternal age was (30.6±5.3) years.There was no difference of these parameters between male and female(P>0.05).2.A multiple regression analysis was performed including following factors: gender, delivery mode, gestational age, birth weight, alimentation mode, serum bilirubin, and maternal age, and none of the evaluated factors was independent influencing factor for plasma NT-proBNP level, with α=0.05 for inspection level.3.Plasma NT-proBNP levels of the 204 preterm infants on day 1, day 3 and day 7 of life followed normal distribution by Shapiro-Wilk test.By repeated measure analysis of variance, the NT-proBNP levels were significantly different on different days (F=443.824, P=0.000). NT-proBNP levels were highest on day 1 of life, and negatively correlated with age in days(r=-0.476, P=0.000). There was significant difference among groups according to different days after birth (t1 d-3 d=4.358, t1 d-7 d=14.743, t3 d-7 d=11.105, respectively; all P=0.000). The levels on day 1, day 3 and day 7 of life were (1875±686) ng/L, (1615±574) ng/L and (1118±380) ng/L, respectively, with 95% confidence interval 530-3220 ng/L, 490-2740 ng/L and 373-1863 ng/L. Conclusions Plasma NT-proBNP levels of early preterm infants are highest on day 1 of life, and negatively correlated with age in days; but not affected by gestational age, gender, birth weight, vaginal delivery or alimentation mode. Key words: Early preterm infants; Plasma; N-terminal pro-brain natriuretic peptide; Reference range