N-Terminal Pro-B-Type Natriuretic Peptide Concentrations Are Markedly Higher in the Umbilical Cord Blood of Newborns than in Their Mothers

Natriuretic peptides are well-established markers in adult heart failure patients (1) and may also be useful for identifying neonates or children with cardiac diseases. Recent studies demonstrated high N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations in healthy neonates with a subsequent rapid decrease within several days (2)(3). However, in the transition from fetal to neonatal life, the physiologic role of natriuretic peptides is not fully understood. Furthermore, it is currently not known whether natriuretic peptides in the fetal circulation derive from the fetus itself or whether there is a placental exchange of maternal natriuretic peptides. The aim of this study, therefore, was to determine the NT-proBNP concentrations in healthy neonates and to compare their concentrations with the values for their respective mothers to indirectly demonstrate a possible placental NT-proBNP exchange. From 100 neonates delivered consecutively between November 2003 and February 2004 (Gynaecologic and Paediatric Hospital Linz), we compared the NT-proBNP concentrations of all healthy vaginally delivered term-born neonates (n = 42) with the NT-proBNP concentrations for their respective healthy mothers. The population characteristics are shown in Table 11 . None of the neonates suffered from asphyxia or respiratory distress syndrome. The study is consistent with the Declaration of Helsinki. Venous umbilical cord blood and peripheral venous blood from the mothers had been drawn for routine blood analyses such as blood grouping. NT-proBNP concentrations in the sample remnants were measured by a sandwich electrochemiluminescence immunoassay (Elecsys 1010; Roche) as described previously (4). The Wilcoxon signed-rank test was used to assess differences in fetal and maternal NT-proBNP concentrations, the Mann–Whitney test was used for gender comparison, and Spearman rank correlation coefficients were calculated. A P value <0.05 was considered statistically significant. Median (25th–75th percentiles) NT-proBNP concentrations [553.4 (413.5–832.9) ng/L] were on average 11.6-fold higher (6.9- to 32-fold) in the cord blood than in the blood samples from the respective mothers [45.5 (22.9–76.8) ng/L; P ≤0.0001; Fig. 11 ]. The NT-proBNP concentrations for the respective mothers and newborns did not correlate (r = −0.11; P = 0.49). There was also no significant difference (P = 0.76) in NT-proBNP concentrations between sexes in the neonates. In this study, we, for the first time, compared NT-proBNP concentrations in a significant number of mothers and their newborn infants immediately after delivery, using a commercially available automated assay. To date, only one small study has compared fetal [mean (SE), 1052.0 (181.5) ng/L] and maternal NT-proBNP concentrations [569.3 (74.0) ng/L] by a RIA (5); the results indicated that NT-proBNP concentrations in healthy fetuses in the 21st week of gestation are twice as high as in maternal blood. The use of different nonstandardized immunoassays, which detect different epitopes and fragments of NT-proBNP, may partly explain the differences between our present study and the previous study. Different gestational ages and the stress of delivery may also influence the secretion patterns of NT-proBNP. Furthermore, the mothers in the study of Walther et al. (5) were not well characterized. In the present study, all mothers were healthy and consequently had low NT-proBNP concentrations. Umbilical venous cord blood NT-proBNP concentrations of neonates are representative of NT-proBNP concentrations in newborns; Mir et al. (2) reported similar NT-proBNP concentrations in the umbilical venous cord blood and peripheral venous blood on the day of delivery. Arterial and venous umbilical cord blood was shown to have similar NT-proBNP concentrations as well (6). Therefore, the high concentrations of natriuretic peptides immediately after delivery may be explained in part by the perinatal circulatory changes from fetus to neonate. After delivery, three important circulatory pathways, the ductus venosus, the foramen ovale, and the ductus arteriosus, are closed, which leads to an increase in pulmonary blood flow in response to lung expansion. Consequently, right ventricular volume and pressure load are increased at birth as well, which may contribute to the peaking of natriuretic peptide concentrations immediately after delivery. Because there was no significant correlation between cord blood and maternal NT-proBNP concentrations, we suggest that there is no placental exchange of NT-proBNP and that increased concentrations in neonates derive from the neonates themselves. Population characteristics (n = 42). Population characteristics (n = 42). NT-proBNP concentrations in newborns and their respective mothers. Box-plots represent the 25th and 75th percentiles (boxes) and minima and maxima (error bars) for each group. ∗, outliers and extreme values; N, number of cases. The NT-proBNP tests were provided by Roche Diagnostics (Austria) free of charge. The company had no influence on study design, data analysis or interpretation, and the content of the manuscript.