Objective Brain natriuretic peptide (BNP) is synthesized in the cardiac ventricles and released in response to volume or pressure load. The aim of the study was to determine whether plasma level of N-terminal pro BNP (NT-pro BNP) can distinguish between cardiac and pulmonary disease (PD) among neonates with respiratory distress (RD). Patients and methods The study included 48 term neonates in the first month of life with signs of RD. They were recruited from Neonatal Intensive Care Unit of Al-Galaa Teaching Hospital. Twenty-six healthy neonates were included as a control group. The degree of RD was assessed using Silverman–Anderson score. Chest X-ray, echocardiography, and laboratory measurement of NT-pro BNP were performed. Results According to the underlying disease, neonates with RD were divided into 28 neonates with PD and 20 neonates with congenital heart disease (CHD). Regardless the etiology of RD, NT-pro BNP was significantly higher in the RD group than in the control ( p = 0.001). There was a significant difference between and within the three groups regarding NT-pro BNP ( p = 0.001). NT-pro BNP was significantly higher in the CHD group than in the PD group ( p = 0.001). There was a significant difference between and within RD subgroups. The NT-pro BNP is a very useful test for identification of CHD in neonates with RD. Area under the receiver operating characteristic curve for CHD was 0.857 ( p = 0.01), sensitivity 66%, specificity 85%, and cutoff point was 24.5 pg/mL. The area under the curve for PD was 0.646 ( p = 0.1) with poor sensitivity and specificity, indicating that NT-pro BNP is a poor test for identification of PD in neonates with RD. Conclusion Term neonates with RD have increased plasma levels of NT-pro BNP. NT-pro BNP is a very good test for identification of CHD in neonates with RD, in comparison with PD. Therefore, plasma NT-pro BNP can be used to differentiate between cardiac and pulmonary cause of RD.

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