Brain-type natriuretic peptide in the diagnosis and management of persistent pulmonary hypertension of the newborn.
OBJECTIVE
The diagnosis of persistent pulmonary hypertension (PPHN) can often be difficult to make, especially in a clinical setting in which pediatric echocardiography is not readily available. A noninvasive test that could differentiate PPHN from other cardiorespiratory disease would be very useful in the early management of the disease, because it would allow rapid identification of those infants at greatest risk of requiring the services of a level 3 nursery. Brain-type natriuretic peptide (BNP) is an endogenous peptide hormone secreted by the cardiac ventricles in response to increased wall stress and related ventricular filling pressures. The purpose of this study was to determine if BNP levels are elevated in newborns with PPHN and therefore may be used as a marker for differentiating PPHN from other forms of respiratory disease during the early newborn period.


METHODS
We used a prospective cohort design with 3 groups. One group was diagnosed with PPHN by clinical and echocardiographic criteria (PPHN group: n = 15). The second group had been diagnosed with respiratory disease; however, PPHN had been ruled out by having no evidence of elevated pulmonary pressure by echocardiography (RD group: n = 17). The third group had no respiratory disease and was breathing room air (RA group: n = 15). BNP levels were measured with a point-of-care fluorescence immunoassay at various time intervals between birth and 150 hours of life.


RESULTS
There were no differences between groups for birth weight, gestational age, gender, race, Apgar scores at 1 minute, or age at time of initial blood sampling. Initial BNP levels (pg/mL) were elevated in the PPHN group relative to both the RA and RD groups (median [25%, 75%]: PPHN group = 1610 [1128, 1745]; RD group = 132 [76, 327]; RA group = 248 [127, 395]). There was no difference in the initial BNP level between the RA and RD groups. BNP levels remained elevated in the PPHN group over both groups for the first 4 days of life. BNP levels correlated with the gradient of the tricuspid regurgitation jet and with the ratio of tricuspid regurgitation jet gradient to mean blood pressure. BNP levels were not affected by administration of dopamine or dobutamine. BNP weakly correlated with the oxygenation index but not with the alveolar-arterial oxygenation gradient.


CONCLUSIONS
Our findings indicate that BNP levels are elevated in infants with PPHN but not in infants with other forms of respiratory distress not associated with PPHN. Elevated BNP levels in term or near-term infants with respiratory distress should increase the suspicion of PPHN. Serial determination may also be helpful in monitoring the clinical course of such infants.
Reynolds
Eric W
EW
Department of Pediatrics, Division of Neonatology, University of Kentucky College of Medicine, 800 Rose St, MS 477, Lexington, KY 40536, USA. ereyn2@uky.edu
Ellington
Jeff G
JG
Vranicar
Mark
M
Bada
Henrietta S
HS
D015415:Biomarkers / Q000097:blood; D001724:Birth Weight; D001794:Blood Pressure; D016022:Case-Control Studies; D015331:Cohort Studies; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007231:Infant, Newborn / Q000097:blood*; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010547:Persistent Fetal Circulation Syndrome / Q000097:blood* / Q000175:diagnosis* / Q000503:physiopathology; D012016:Reference Values; D012131:Respiratory Insufficiency / Q000097:blood* / Q000175:diagnosis / Q000503:physiopathology; D012680:Sensitivity and Specificity; D014556:Urine
D015415:Biomarkers; D020097:Natriuretic Peptide, Brain