Early N-Terminal Pro B-Type Natriuretic Peptide (NTproBNP) Plasma Values and Associations with Patent Ductus Arteriosus Closure and Treatment-An Echocardiography Study of Extremely Preterm Infants

Abstract

The aim was to investigate the association of gestational age (GA), echocardiographic markers and levels of plasma N-terminal pro-B-type natriuretic peptide (NTproBNP) with the closure rate of a haemodynamically significant patent ductus arteriosus (hsPDA). Ninety-eight Swedish extremely preterm infants, mean GA 25.7 weeks (standard deviation 1.3), born in 2012-2014, were assessed with echocardiography and for levels of NTproBNP. Thirty-three (34%) infants had spontaneous ductal closure within three weeks of age. Infants having spontaneous closure at seven days or less had significantly lower NTproBNP levels on day three, median 1810 ng/L (IQR 1760-6000 ng/L) compared with: infants closing spontaneously later, 10,900 ng/L (6120-19,200 ng/L); infants treated either with ibuprofen only, 14,600 ng/L (7740-28,100 ng/L); or surgery, 32,300 ng/L (29,100-35,000 ng/L). Infants receiving PDA surgery later had significantly higher NTproBNP values on day three than other infants. Day three NTproBNP cut-off values of 15,001-18,000 ng/L, predicted later PDA surgery, with an area under the curve in ROC analysis of 0.69 (0.54-0.83). In conclusion, the spontaneous PDA closure rate is relatively high in extremely preterm infants. Early NTproBNP levels can be used with GA in the management decisions of hsPDA.

Keywords: N-terminal pro B-type natriuretic peptide; cardiac troponin T; echocardiography; extremely preterm; patent ductus arteriosus.

Figure 1

Flow chart of the study showing inclusion and exclusion.

Figure 2

(a) The cumulative probability of PDA closure for all the infants (N = 98) is shown with a K-M survival curve with 95% CB. Infants are divided into those born before 25 weeks of GA and those born at or later than 25 weeks GA. The analysis time was until 133 days of age as then all the infants had reached 40 weeks postmenstrual age. The censoring protocol is shown in Supplemental Table S3. (b) The cumulative probability of PDA closure for infants who either were not treated or only treated with ibuprofen is shown in a K-M survival curve with 95% CB. Infants that later died, were transferred or underwent PDA surgery were excluded (N = 60). The analysis time was until 133 days of age as then all the infants had reached 40 weeks postmenstrual age. The censoring protocol is shown in Supplemental Table S3. Abbreviations: PDA: patent ductus arteriosus; K-M: Kaplan-Meier; trx: treatment; Ibu: ibuprofen, CB: confidence bands.

Figure 3

(a) The ROC curve is shown for the NTproBNP value on day three in predicting later spontaneous ductal closure in extremely preterm infants (N = 80). Abbreviations: ROC: receiver operating characteristics; NTproBNP: N-terminal pro B-type natriuretic peptide. (b) The ROC curve is shown for the NTproBNP value on day three in predicting later PDA surgery in extremely preterm infants (N = 80). Abbreviations: PDA: patent ductus arteriosus; NTproBNP: N-terminal pro B-type natriuretic peptide; ROC: receiver operating characteristics.