PEDIATRICS Vol. 114 No. 5 November 2004, pp. 1297-1304 (doi:10.1542/peds.2004-0525)
Brain-Type Natriuretic Peptide in the Diagnosis and Management of Persistent Pulmonary Hypertension of the Newborn
From the Department of Pediatrics, University of Kentucky College of Medicine, Lexington, Kentucky
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ABSTRACT |
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 TOP ABSTRACT METHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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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.
Method. 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.
Key Words: B-type natriuretic peptide • persistent pulmonary hypertension of the newborn
Abbreviations: PPHN, persistent pulmonary hypertension • BNP, brain-type natriuretic peptide • RD, respiratory distress • RA, room air • NICU, neonatal intensive care unit • HOL, hour(s) of life • PDA, patent ductus arteriosis • ECMO, extracorporeal membrane oxygenation • DOL, day(s) of life • A-a DO2, alveolar-arterial oxygen pressure gradient • OI, oxygenation index • TR, tricuspid regurgitation jet • MBP, mean blood pressure • ANP, atrial natriuretic peptide • NT-PROBNP, N-terminal-Pro-BNP
Persistent pulmonary hypertension (PPHN) is a disease of term and near-term newborns in which the pulmonary vascular resistance remains elevated during the neonatal period. The clinical presentation often resembles other cardiorespiratory diseases. Therefore, it is often difficult to make the correct diagnosis rapidly, which can delay appropriate treatment. This is a problem particularly in hospitals in which pediatric echocardiography is not readily available. A noninvasive test that could rapidly differentiate PPHN from other cardiorespiratory disease would be helpful in the early management of this disease.
Brain-type natriuretic peptide (BNP) is an endogenous peptide hormone that is secreted by the cardiac ventricles in response-increased wall stress and related ventricular filling pressure. BNP levels are used in adult patients to evaluate congestive heart failure. We hypothesize that BNP levels will be elevated in infants with PPHN when compared with infants with other cardiorespiratory diseases. Normal levels of BNP have not been previously established in newborns.
The objectives of this research project are to determine normal levels of BNP in term and near-term newborns and evaluate BNP as proteomic marker for identifying and managing infants with PPHN. The hypothesis to be tested is that there is a correlation between BNP and PPHN in term and near-term newborns that can be used to aid in the management of infants with PPHN. If our hypothesis proves to be true, BNP levels could be used as a quick and inexpensive tool to help differentiate PPHN from other respiratory disease, monitor the disease progression, and predict outcome.
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METHODS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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Study Design
This was a prospective cohort study. Two groups of control infants were identified. One group included term and near-term newborns with respiratory distress (RD) but no clinical or echocardiographic evidence of PPHN. A second group of infants had no RD and were breathing room air (RA). A third group (PPHN) included infants with PPHN diagnosed by having hypoxemia and evidence of elevated pulmonary artery pressure by echocardiography. Patients with evidence of structural cardiac disease or genetic anomalies were excluded. All infants were admitted to the University of Kentucky Chandler Medical Center neonatal intensive care unit (NICU) or normal newborn nursery from January through December of 2003. The study was approved by the institutional review board of the University of Kentucky, and informed consent was obtained from the parents of all participants. The study met all applicable Health Insurance Portability and Accountability Act (HIPAA) standards.
Control infants were identified when blood was to be drawn for other reasons not related to this study. After being identified, parents were approached for informed consent and enrollment in the study. Blood was collected from control infants depending on when blood sampling was indicated for their clinical management. Samples were collected from case infants on enrollment and then at least daily until the symptoms of PPHN had resolved. The protocol did not allow for specification of a rigid interval between samples, because we were collecting BNP samples only when the infants had blood drawn for clinical reasons. No infant, case or control, received additional needle or heel sticks as a result of this study over and above what was required for management of the infant's specific condition. Serial determination of BNP was discontinued at 150 hours of life (HOL), because control infants very infrequently required blood drawing beyond that age. Data collected from this study were not used to influence medical decision-making. Management of each infant was left to the discretion of the attending physician.
Echocardiography was performed as part of the infants' medical care, or in some cases an echocardiogram was provided at no cost to the patient to document normal pulmonary pressure. PPHN was defined as hypoxemia with echocardiographic findings of systemic or higher right ventricular pressure and/or right-to-left shunting at a patent foramen ovale or patent ductus arteriosis (PDA). All infants in the PPHN group had echocardiograms. Fourteen of 17 in the RD group and 3 of 15 in the RA group also had an echocardiogram. There was no reason to suspect PPHN in the RA group by clinical criteria; therefore, an echocardiogram was not clinically indicated. In the RD group, the 3 infants who did not have an echocardiogram responded quickly to minimal treatment, requiring only supplemental oxygen delivered by a hood for a few hours. Because some of these echocardiograms were provided outside of the usual medical care, physicians interpreting the echocardiograms were not blinded to the BNP levels or group assignment.
Demographic data collected included postmenstrual age at delivery, gender, race, birth weight, perinatal history, and associated diagnoses. At each blood sampling, data collected included BNP level, collection time, postnatal age at the time of sample collection, mode of sample collection (arterial, venous, or capillary), most recent estimation of pulmonary artery pressure by echocardiography (when available), most recent blood gas analysis (when available), current ventilator settings, and requirement for nitric-oxide treatment or extracorporeal membrane oxygenation (ECMO).
BNP Measurements
BNP levels were measured with a commercially available point-of-care fluorescence immunoassay (Triage Meter Plus, Biosite Inc, San Diego CA) in the NICU. Blood was collected from the infant into a standard blood sample collection vial with ethylenediamine tetraacetic acid ("purple" or "lavender" top Microtainer, Becton Dickinson Inc, Franklin Lakes, NJ). Samples were run immediately after collection by either the principal investigator (E.W.R.) or 1 of the NICU fellows. Samples were collected from arterial or venous catheters or by mixed capillary samples (heel stick).
Statistics
The lack of established normal values for term newborns and those with RD rendered calculation of sample size difficult. Yoshibayashi et al1 found a level of 56.7 ± 49.6 fmol/mL at birth in 18 term infants. Ikemoto et al2 suggested a level of 41.8 ± 10.1 pg/mL in 10 infants born before 36 weeks' gestation. BNP levels >400 pg/mL are considered diagnostic of heart failure in adults. For the primary outcome, BNP levels with or without PPHN and an assumption of an expected difference of 20% to 30% with an SD of ± 10 pg/mL, at a power of 0.8 and 
of 0.05, we estimated that 
10 patients would be needed in each group. Statistical analysis was performed with Sigma Stat for Windows 2.0 (Jandel Corporation, San Rafael, CA).
Statistical methods included analysis of variance when comparing many groups followed by an appropriate multiple-comparison test if significance was found. Fischer's exact test and linear regression were used for comparing groups and measuring correlations where appropriate. Analysis of variance was used for comparing BNP levels over time. Spearman's rank-sum test was used to correlate BNP with measures of pulmonary pressure.
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RESULTS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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Demographics
The demographic information for the study participants is shown in Table 1. There were no differences among the groups for birth weight, gestational age, gender, race, Apgar scores at 1 minute, or age at the time of first blood sampling. The median Apgar score at 5 minutes was statistically higher in the RA group (9) over both the RD and PPHN groups (8). Diagnoses in the RD group include transient tachypnea of the newborn (7), RD syndrome (3), pneumothorax (3), possible sepsis (2), and meconium aspiration (2). Diagnoses in the RA group include delayed transition (6), hypo-/hyperglycemia (2), hyperbilirubinemia (2), sepsis (2), feeding intolerance (1), volvulus (1), and bloody stools (1). Of the PPHN group, 4 infants had meconium-aspiration syndrome, 3 had birth asphyxia, and 2 had positive blood cultures during sepsis evaluations. The remaining 6 infants did not have an obvious identifiable risk factor for PPHN.
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In the RD group, 9 infants required supplemental oxygen delivered by Oxyhood. Eight were intubated and required mechanical ventilation, with 7 of those on intermittent mandatory ventilation and 1 on high-frequency oscillatory ventilation. One infant also was given nitric-oxide therapy. In the PPHN group, 6 of the infants required supplemental oxygen delivered by Oxyhood only. The remaining 9 were intubated and required mechanical ventilation. Of these, 4 were on intermittent mandatory ventilation only. Five were on high-frequency oscillatory ventilation. Five infants required nitric-oxide therapy, and 1 required ECMO. No study infants died during the study period.
Initial BNP Levels
The mean age at initial sample collection (HOL) was not different for the 3 groups (RD = 25.6 ± 3.3; RA 28.7 ± 5.0; PPHN 19.3 ± 3.1). Initial BNP levels (pg/mL) were significantly elevated in the PPHN group relative to both the RA and RD groups (median [25%, 75%] analysis of variance on ranks, posthoc Dunn's test: PPHN = 1610 [1128, 1745]; RD = 132 [76, 327]; RA = 248 [127, 395]). These results are shown on Fig 1.
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An initial BNP level >550 pg/mL was predictive of PPHN (P < .001) with sensitivity of 83% and specificity of 100%. All infants in this study with initial BNP levels >835 pg/mL had PPHN.
BNP Levels Over Time
The median highest BNP levels on each day of life (DOL) for each group are shown in Fig 2. The median highest BNP levels (pg/mL) on DOL 1 for the RD, RA, and PPHN groups were 263, 379, and 1379, respectively. There was no difference between the RA and RD groups. The PPHN group was significantly elevated over both the RA and RD groups. BNP levels remained elevated in the PPHN group over both the RD and RA groups up to and including DOL 3 (P 
.001 for each day). On DOL 4, 5, and 6, there were trends toward significant differences in BNP levels among the 3 groups. However, the low number of samples in the RA and RD groups makes it difficult to make definitive statements about the relationships between the groups. There were no differences noted between the RA and RD groups for any DOL in the study period.
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BNP Levels and Monitoring Clinical Course
In several of our patients, after initial BNP levels were measured, a worsening clinical condition was associated with an increase in BNP levels. Figure 3 shows an example of such a case. This infant was enrolled with an initial BNP level of 554 pg/mL. Initially, the level decreased. However, at 40 HOL he became acutely worse and required nitric-oxide therapy (open circles denote nitric-oxide therapy). As he worsened, his BNP level was nearly triple the initial level. This phenomenon was noticed in a few of the infants with PPHN.
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BNP Levels With Blood Pressure Support
In the PPHN group, 8 infants required dopamine and/or dobutamine for blood pressure support. Initial BNP levels (pg/mL) for these infants were not different from those infants with PPHN who were not given these medications (mean [SEM]: 1680.0 [500.7] with pressors and 1638.6 [256.7] without pressors). We also looked at all BNP measurements for these same infants over the entire study period and found no difference between the 2 groups (mean [pg/mL] ± SEM: 624.2 ± 100.2 with pressors and 841.1 ± 126.0 without pressors [t test]).
BNP Levels and Measures of Disease Severity
To determine if BNP levels correlate with disease severity, we compared BNP levels to both the alveolar-arterial oxygen pressure gradient (A-a DO2) and the oxygenation index (OI) when these measurements were available. BNP levels were available for 136 A-a DO2 measurements and 86 OI calculations. There was no correlation found between BNP and A-a DO2. There was a statistically significant correlation between BNP and OI (P = .044, Spearman's rank-sum test). However, the correlation was quite weak (rs = 0.218).
BNP Levels and Pulmonary Pressure
To compare BNP levels to pulmonary pressure, we measured the gradient of the tricuspid regurgitation jet (TR) and also calculated the ratio of TR to mean blood pressure (TR/MBP) for the initial echocardiogram of the participants. Results are shown in Fig 4. There was a statistically significant correlation between BNP and TR (P < .0001; rs = 0.830; n = 32 [Spearman's rank-sum test]). Likewise, there was a statistically significant correlation between BNP and TR/MBP (P < .0001; rs = 0.804; n = 30 [Spearman's rank-sum test]). Some infants had >1 echocardiogram during the study period. Results were similar when all the echocardiograms were analyzed together. Because the measurement of TR gradient is not continuous at low pulmonary pressures (TR gradients less than right atrial pressure do not generate a jet and are therefore measured as 0), the correlation is likely higher than can be measured with echocardiographic estimates of pulmonary pressure. Direct measurement of pulmonary pressure is possible by cardiac catheterization but has the disadvantage of being an invasive procedure and not suitable for this research.
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BNP Levels and Sample Type
The instrument manufacturer cautions that severe hemolysis can interfere with BNP measurement. Unfortunately, most blood drawing in relatively well newborns is done by mixed capillary collection (heel stick). Therefore, hemolysis is a common problem. To determine if this would interfere with our measurements, we tracked the sample type (arterial, venous, or capillary) for each collection. No difference was noted within the RA and PPHN groups for the 3 sampling techniques. In the RD group, measurements from arterial samples did not differ from those obtained from capillary samples but were statistically higher than venous samples. However, there were only a few (n = 4) venous samples to compare with 50 arterial and 19 capillary samples.
BNP Levels and Urine Output
Because BNP is cleared by renal filtration as well as receptor-mediated clearance and proteolysis by endopeptidase, urine output (mL/kg per hour) was measured for the 4- and 8-hour intervals before the initial BNP measurement. No correlation was found between BNP level and either the 4- or 8-hour measurement by linear regression (4-hour interval: n = 29, m = 1.87 pg/mL/mL/kg per hour, r2 = 0.00007, P = .97; 8-hour interval: n = 27, m = –56.4 pg/mL/mL/kg per hour, r2 = 0.32, P = .48). Also, there was no correlation when the measurements were divided by group.
BNP Levels and Ventricular Function
Ventricular function was evaluated by measuring the fractional shortening of the ventricles (percentage shortening) by echocardiography. BNP levels were correlated with the fractional shortening measurement of the initial echocardiogram. Because our protocol did not allow for additional blood drawing, we could not control the time interval between the echocardiogram and sample collection. However, in most cases, particularly in the PPHN group, the infants were receiving frequent (hourly) blood drawings. Therefore, it is not likely that a significant delay occurred. No correlation was noted (n = 27, m = 20.4 pg/mL/% shortened, r2 = 0.01, P = .55).
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DISCUSSION |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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PPHN can present with symptoms similar to cardiovascular shock, with infection and cyanotic heart lesions leading the differential diagnosis. Often, the diagnosis can remain in doubt until an echocardiogram can be performed and the pulmonary artery pressure can be estimated. This is a problem particularly in hospitals that do not have pediatric echocardiography readily available. More precise measurement of pulmonary artery pressure could be determined by cardiac catheterization, but because of the invasiveness of this procedure, it is rarely performed on newborn infants except in preparation for surgical correction of heart defects. Even with a normal echocardiogram, a small number of infants go on to develop signs and symptoms of PPHN and have a favorable response to nitric-oxide therapy. Still other infants have respiratory disease that clinically mimics PPHN; however, they do not respond to treatments such as hyperventilation or nitric oxide. Prompt identification of infants with PPHN is important because (1) a delay in appropriate treatment can contribute to a worse prognosis and increase the likelihood of requiring extreme measures such as nitric oxide or ECMO, and (2) inappropriate treatment of PPHN will increase the risk to the patient without producing measurable benefits. The treatment of PPHN includes hyperventilation, often to very low PCO2 (partial pressure of carbon dioxide) levels, alkalinization to pH levels >7.40, and extremely slow weaning from ventilatory support. These strategies are very different from the management of other diseases of newborn infants, in which higher PCO2 and lower pH values are tolerated and extubation is attempted at the earliest safe occasion. ECMO is used as rescue therapy for the most severe cases. A minimally invasive test that could differentiate PPHN from other respiratory diseases would be very helpful when echocardiography is not readily available, in that it could allow quicker identification of infants suspected of having the disease and prompt appropriate treatment or transfer to a tertiary care facility. It also may identify those infants who will not respond to typical treatments for PPHN. This could potentially obviate the need for a trial of nitric oxide, which can cost as much as $3000 a day. Furthermore, this kind of test may be helpful also in monitoring response to treatment and disease progression or improvement.
Natriuretic peptides are endogenous peptide hormones released by the heart in response to stress. There are several types of natriuretic peptides synthesized by the human body. The 2 about which we know the most are atrial natriuretic peptide (ANP) and BNP. ANP has been widely studied in adults and children. Information on BNP in children is relatively scarce. BNP was first identified (in 1988) in the brains of piglets, from which it gets the name, but was later found to be secreted predominantly from the heart ventricles.3 The circulating and storage form is a 17-amino acid residue ring structure formed by a disulfide bridge, with 9-residue N-terminal and 6-residue C-terminal extensions.4 The synthesis, secretion and clearance of BNP are different from those of ANP, suggesting that BNP does not duplicate the function of ANP.5 BNP is secreted by the cardiac ventricles in response to stress. This stress may be ventricular wall expansion, pressure overload, or increased wall tension. BNP aids in the regulation of systemic blood pressure by countering the effects of the renin-angiotensin and other vasoconstricting neurohormonal systems through a cyclic guanosine monophosphate second messenger. BNP levels have been shown in adults to correlate with disease severity and outcome prediction in patients with an established diagnosis of heart failure.6, 7 BNP does not cross the placenta, and therefore levels in infants are not affected by maternal disease, even those that result in elevated maternal BNP levels. Low levels of BNP can be detected in umbilical blood at delivery.1, 8 There is a surge to >20 times the umbilical blood level shortly after birth, and levels decrease to near adult levels by 3 months of life. BNP levels have been shown to be elevated in preterm infants with PDA.9–11 These levels decrease as the PDA closes. Also, a linear relationship between BNP levels and pulmonary pressure in preterm infants has been suggested.2 To date, little data are available on BNP levels in term infants, and no BNP measurements have been made in infants affected by PPHN.
It has been shown that the precursor molecule, N-terminal-Pro-BNP (NT-PROBNP), is a more sensitive and specific marker for ventricular dysfunction than the biologically active form of BNP, and NT-PROBNP remains stable in refrigerated blood samples for later analysis.8, 12, 13 However, PPHN is not necessarily associated with ventricular dysfunction, and our samples were run immediately after sampling on a commercially available point-of-care instrument. Also, BNP levels can be readily measured in most hospitals in the United States with the equipment used in this study. The particular instrument that we used is already widely available to most physicians and is used in many emergency departments to rapidly evaluate adult patients with congestive heart failure. To our knowledge, there is no commercially available equipment for measuring NT-PROBNP at this time.
The results of this study show that BNP levels are elevated in infants with PPHN relative to those with RD without associated PPHN. However, BNP levels did not seem to correlate with disease severity as measured by the A-a DO2 and only correlated weakly with OI. There is a highly significant correlation of BNP levels with the gradient of the TR as well as between BNP and the ratio of TR to systemic pressure. BNP levels were minimally affected by the method of collection (arterial, venous, or capillary). These minor differences may not be clinically relevant, because most infants in whom the diagnosis is in question will have central access for blood drawing. The manufacturer, however, cautions about hemolysis interfering with the BNP levels. Theoretically, any hemolytic disease in the newborn may give falsely elevated values. BNP levels were not affected by the use of dopamine or dobutamine. An increasing BNP level was often temporally related to worsening clinical symptoms and a need for additional pharmacologic and/or ventilatory interventions.
BNP is a marker of ventricular stress. Therefore, the results of this study should not be interpreted as showing that BNP levels are diagnostic of PPHN or that measuring BNP levels can be used in place of echocardiography. Infants with congenital heart disease were excluded from this study. However, we suspect that BNP levels may be elevated in some forms of structural disease. Cardiac anomalies that result in ventricular stress, such as pulmonary or aortic atresia or stenosis, may have increased serum BNP levels. However, theoretically, not all structural heart disease would be associated with ventricular stress and elevated BNP levels. Therefore, BNP levels should not be used in place of an echocardiogram and thorough cardiac evaluation. However, elevated BNP levels may indicate a need to transfer an infant to a tertiary care facility at which pediatric echocardiography and appropriate intensive care services are available.
It is interesting to note that the BNP levels in our RA control infants are much higher than the normal levels found in adults. We suspect that this is because of the transitional circulation that is present in the neonatal period. During gestation, the right ventricle carries relatively less blood than it does after delivery. Any blood flow that does traverse the right ventricle meets with low resistance and therefore relatively low pressure because of the PDA and the presence of placental circulation. After delivery, the normal changes induced in the newborn infant cause an increase in ventricular wall stress on both the pulmonary and systemic sides, leading to an increase in BNP. In this study, newborns in the control groups achieved steady BNP levels near normal adult range by 60 HOL. Indeed, these findings are consistent with the work of other authors who have shown a rapid increase in natriuretic peptides after birth followed by a decrease to steady levels over the course of 2 to 3 days.1, 8 It is suggested that the increase in natriuretic peptides that accompanies delivery in normal newborns may be an attempt to decrease ventricular preload in the first DOL. This information along with our findings may suggest a role for new pharmacologic interventions for PPHN.
It should be noted that the investigator was not blinded to the group assignment or the BNP level. Likewise, the echocardiography technician and pediatric cardiologist were not always blinded to the BNP level or group assignment. Obviously, when an echocardiogram was performed at no charge and outside of medical necessity, the cardiologist would suspect the infant to be assigned to 1 of the control groups, which was unavoidable. However, both the BNP level and estimation of pulmonary pressure are objective measurements that should limit the impact of any bias introduced by this method. It may be noted also that our study population has an overwhelming number of white males, and therefore results may not be appropriate for all populations. However, there were no differences for gender or race across the 3 groups in the study, and PPHN does tend to be a disease of white males. More study is required to identify all the possible nuances of BNP and investigate other proteomic techniques for the diagnosis and management of newborn disease states.
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CONCLUSIONS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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BNP levels were found to be elevated in infants with PPHN relative to infants with noncardiac causes of RD. In this study population, initial BNP levels >850 pg/mL were found only in the PPHN group. A rising BNP level may be a more important marker of disease severity than the actual amount of BNP present (similar to PSA in adult prostate cancer). BNP levels correlate with echocardiographic estimates of pulmonary pressure but not with clinical measures of disease severity. BNP measurements are not affected by blood pressure medications, urine output, or ventricular function. BNP level is a sensitive proteomic marker that can be used as an adjunct to other clinical and laboratory information in making the diagnosis of PPHN, especially in an institution that cannot obtain a pediatric echocardiogram rapidly. Physicians should have increased suspicion of PPHN, or other states of ventricular stress, when caring for a term or near-term newborn with RD and an elevated BNP level. This information may be helpful in determining if a particular infant requires early transfer to a tertiary care facility.
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ACKNOWLEDGMENTS |
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This project was funded from the institutional K-30 Scholars program at the University of Kentucky (K30-HL004163; E.W.R.).
We thank Scott Mader of Biosite Inc for the generous donation of equipment necessary to complete this research. We also thank the neonatal intensive care unit Fellows and echocardiography technicians who helped with this project.
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FOOTNOTES |
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Accepted May 19, 2004.
Reprint requests to (E.W.R.) Department of Pediatrics, Division of Neonatology, University of Kentucky College of Medicine, 800 Rose St, MS 477, Lexington, KY 40536. E-mail: ereyn2{at}uky.edu
Biosite Inc donated the equipment necessary for this research but gave no financial support and had no input into the study design or data analysis.
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REFERENCES |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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- Yoshibayashi M, Kamiya T, Saito Y, et al. Plasma brain natriuretic peptide concentrations in healthy children from birth to adolescence: marked and rapid increase after birth.
Eur J Endocrinol. 1995;133
:207
–209
[Abstract/Free Full Text] - Ikemoto Y, Nogi S, Teracuchi M, Kojima T, Hirata Y, Kobayashi Y. Early changes in plasma brain and atrial natriuretic peptides in premature infants: correlation with pulmonary arterial pressure. Early Hum Dev. 1996;46 :55 –62[CrossRef][Web of Science][Medline]
- McDowell G, Shaw C, Buchanan KD, Nicholls DP. The natriuretic peptide family. Eur J Clin Invest. 1995;25 :291 –298[Web of Science][Medline]
- Yandle T. Biochemistry of natriuretic peptides. J Intern Med. 1994;235 :561 –576[Web of Science][Medline]
- Furuhashi N, Kimura H, Nagae H, Yajima A, Kimura C, Saito T. Brain natriuretic peptide and atrial natriuretic peptide levels in normal pregnancy and preeclampsia. Gynecol Obstet Invest. 1994;38 :73 –77[Web of Science][Medline]
- Bettencourt P, Ferreira S, Azevedo A, Ferreira A. Preliminary data on the potential usefulness of B-type natriuretic peptide levels in predicting outcome after hospital discharge in patients with heart failure. Am J Med. 2002;113 :215 –219[CrossRef][Web of Science][Medline]
- Maisel A. B-type natriuretic peptide levels. Cardiovasc Toxicol. 2001;1 :159 –164[CrossRef][Medline]
- Mir TS, Laux R, Hellwege HH, et al. Plasma concentrations of aminoterminal pro atrial natriuretic peptide and aminoterminal pro brain natriuretic peptide in healthy neonates: marked and rapid increase after birth.
Pediatrics. 2003;112
:896
–899
[Abstract/Free Full Text] - Holstrom H, Hall C, Thaulow E. Plasma levels of natriuretic peptides and hemodynamic assessment of patent ductus arteriosus in preterm infants. Acta Paediatr. 2001;90 :26 –33
- Holstrom H, Omland T, Editorial Board. Natriuretic peptides as markers of patent ductus arteriosus in preterm infants. Clin Sci (Lond). 2002;103 :79 –80[Medline]
- Puddy VF, Amirmansour C, Williams AF, Singer DR. Plasma brain natriuretic peptide as a predictor of haemodynamically significant patent ductus arteriosus in preterm infants. Clin Sci (Lond). 2002;103 :75 –77[Medline]
- Daggubati S, Parks JR, Overton RM, Cintron G, Schocken DD, Vesell DL. Adrenomedullin, endothelin, neuropeptide Y, atrial, brain, and C-natriuretic prohormone peptides compared as early heart failure indicators [published correction appears in Cardiovasc Res. 1999;44:452–453].
Cardiovasc Res. 1997;36
:246
–255
[Abstract/Free Full Text] - Hunt PJ, Yandle TG, Nichols MG, Richards AM, Espiner EA. The amino-terminal pro-brain natriuretic peptide (NT-PROBNP): a new marker of cardiac impairment. Clin Endocrinol (Oxf). 1997;47 :287 –296[CrossRef][Medline]
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A. El-Khuffash and E. J Molloy Are B-type natriuretic peptide (BNP) and N-terminal-pro-BNP useful in neonates? Arch. Dis. Child. Fetal Neonatal Ed., July 1, 2007; 92(4): F320 - F324. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. L. da Graca, D. C. Hassinger, P. A. Flynn, C. P. Sison, M. Nesin, and P. A.M. Auld Longitudinal changes of brain-type natriuretic Peptide in preterm neonates. Pediatrics, June 1, 2006; 117(6): 2183 - 2189. [Abstract] [Full Text] [PDF]
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|
E. W. Reynolds Brain-Type Natriuretic Peptide in the Diagnosis and Management of Persistent Pulmonary Hypertension of the Newborn: In Reply Pediatrics, April 1, 2005; 115(4): 1112 - 1112. [Full Text] [PDF]
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|
|
M. J. Baptista, J. Correia-Pinto, G. Rocha, H. Guimaraes, and J. C. Areias Brain-Type Natriuretic Peptide in the Diagnosis and Management of Persistent Pulmonary Hypertension of the Newborn Pediatrics, April 1, 2005; 115(4): 1111 - 1111. [Full Text] [PDF]
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