natriuretic-peptide--brain and Hernias--Diaphragmatic--Congenital

Natriuretic peptides (NP) are released from the heart in response to pressure and volume overload. The biologic properties of NPs include counterregulation of the rennin-angiotensin-aldosterone pathway and a decrease in sympathetic tone resulting in diuresis, natriuresis, and vasodilation. Natriuretic peptides help to maintain fluid balance and blood pressure in a healthy physiologic range. The B-type natriuretic peptide (BNP) and its N-terminal precursor (NTpBNP) have become important diagnostic biomarkers of cardiovascular diseases (CVDs) in adults. Although many studies suggest that BNP also is a reliable test for diagnosing significant CVDs in children, data are lacking on whether additional use of BNP increases diagnostic accuracy and predicts prognosis. This comprehensive review describes the utility of BNP and NTpBNP for various CVDs of the neonatal and pediatric age groups. Because BNP is not a stand-alone test, it should not replace history, physical examination, or clinical judgment, but it has a clear value in adding details to the whole story for children, thus enabling the front-line physicians to make a diagnosis, especially in the acute care setting.

Topics: Adolescent; Biomarkers; Cardiac Surgical Procedures; Cardiovascular Diseases; Child; Child, Preschool; Heart Defects, Congenital; Heart Transplantation; Hernia, Diaphragmatic; Hernias, Diaphragmatic, Congenital; Humans; Infant; Infant, Newborn; Natriuretic Peptide, Brain

Biomarkers may be helpful in prediction of outcomes of infants with congenital diaphragmatic hernia. The predictive value of high-sensitivity troponin T and N-terminal pro-brain natriuretic peptide was investigated in 128 infants with congenital diaphragmatic hernia. After correction for multiple testing, those biomarkers did not predict severe pulmonary hypertension, death, need of extracorporeal membrane oxygenation, or bronchopulmonary dysplasia.. Netherlands Trial Registry: 1310.

Topics: Biomarkers; Bronchopulmonary Dysplasia; Extracorporeal Membrane Oxygenation; Female; Hernias, Diaphragmatic, Congenital; Humans; Hypertension, Pulmonary; Infant, Newborn; Male; Natriuretic Peptide, Brain; Netherlands; Prognosis; Prospective Studies; Severity of Illness Index; Troponin T

To evaluate the prognostic information derived from the daily measurements of N-terminal pro-B-type natriuretic peptide (proBNP) in neonates with congenital diaphragmatic hernia undergoing extracorporeal life support (ECLS).. Plasma proBNP was prospectively measured daily during the first week of ECLS using an electrochemiluminescence immunoassay. Patients (n = 63) were allocated according to outcome: survivors (group 1, n = 35); nonsurvivors with successful weaning (defined as survival for >12 hours after ECLS discontinuation) (group 2, n = 16); nonsurvivors with unsuccessful weaning (group 3, n = 12). ProBNP kinetics were compared using Kruskal-Wallis testing and correlated with pulmonary hypertension and cardiac dysfunction on echocardiography using the Spearman correlation coefficient.. Infants in group 3 presented significantly higher proBNP values from day 3 to day 6 compared with group 1 and 2. Overall mortality among patients with the highest proBNP values on day 1 was 30.6% compared with 63% in those patients with at least 1 higher value on day 2 to day 7. In patients with a late increase (day 4 to day 7) in proBNP the mortality was 70%, compared with 32.6% in those with proBNP below the value on day 1. Weaning failure was 35% in patients with a late increase and 11.6% in those without a late increase. ProBNP correlated significantly with pulmonary hypertension and cardiac dysfunction before and during ECLS.. Absolute proBNP values are associated with weaning failure but not overall mortality in neonates with congenital diaphragmatic hernia undergoing ECLS. Echocardiographic findings correlate well with proBNP values.

Topics: Biomarkers; Echocardiography; Extracorporeal Membrane Oxygenation; Female; Hernias, Diaphragmatic, Congenital; Humans; Infant, Newborn; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies

To evaluate B-type natriuretic peptide (BNP) as a longitudinal biomarker of clinical outcome in infants with congenital diaphragmatic hernia (CDH).. We conducted a retrospective study of 49 infants with CDH, classifying the cohort by respiratory status at 56 days, based on a proposed definition of bronchopulmonary dysplasia for infants ≥32 weeks' gestation: good outcome (alive with no respiratory support) and poor outcome (ongoing respiratory support or death). BNP levels were available at age 1-5 weeks. Longitudinal BNP trends were assessed using mixed-effects modeling. Receiver operating characteristic curves were generated to identify BNP cutoffs maximizing correct outcome classification at each time point. The time to reach BNP cutoff by outcome was assessed using Kaplan-Meier curves for weeks 3-5.. Twenty-nine infants (59%) had a poor outcome. Infants with a poor outcome were more likely than those with a good outcome to have liver herniated into the thorax (90% vs 50%; P = .002) and to undergo nonprimary repair (93% vs 35%; P < .001). Mixed-effects modeling demonstrated a differing decline in BNP over time by outcome group (P = .003 for interaction). BNP accurately predicted outcome at 3-5 weeks (area under the curve, 0.81-0.82). BNP cutoffs that maximized correct outcome classification decreased over time from 285 pg/mL at 3 weeks to 100 pg/mL at 4 weeks and 48 pg/mL at 5 weeks. Time to reach the cutoffs of 100 pg/mL and 48 pg/mL were longer in the poor outcome group (log-rank P = .006 and <.0001, respectively).. Elevated BNP accurately predicts poor outcome in infants with CDH at age 3-5 weeks, with declining cutoffs over 3-5 weeks of age.

Topics: Biomarkers; Female; Hernias, Diaphragmatic, Congenital; Humans; Infant; Infant, Newborn; Male; Natriuretic Peptide, Brain; Predictive Value of Tests; Respiration, Artificial; Retrospective Studies; Treatment Outcome

Topics: Extracorporeal Membrane Oxygenation; Hernias, Diaphragmatic, Congenital; Humans; Infant; Natriuretic Peptide, Brain

Topics: Hernias, Diaphragmatic, Congenital; Humans; Infant; Natriuretic Peptide, Brain

Topics: Heart Diseases; Hernias, Diaphragmatic, Congenital; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Peptide Fragments

Topics: Heart Diseases; Hernias, Diaphragmatic, Congenital; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Peptide Fragments

Cardiac dysfunction is a key determinant of outcome in congenital diaphragmatic hernia (CDH). Pro-b-type natriuretic peptide (proBNP) is used as a prognosticator in heart failure and cardiomyopathy. We hypothesized that proBNP levels would be associated with ventricular dysfunction and high-risk disease in CDH.. Patients in the CDH Study Group (CDHSG) from 2015-2019 with at least one proBNP value were included. Ventricular function was determined using echocardiograms from the first 48 h of life.. A total of 2,337 patients were identified, and 212 (9%) had at least one proBNP value. Of those, 3 (1.5%) patients had CDHSG stage A defects, 58 (29.6%) B, 111 (56.6%) C, and 24 (12.2%) D. Patients with high-risk defects (Stage C/D) had higher proBNP compared with low-risk defects (Stage A/B) (14,281 vs. 5,025, p = 0.007). ProBNP was significantly elevated in patients who died (median 14,100, IQR 4,377-22,900 vs 4,911, IQR 1,883-9,810) (p<0.001). Ventricular dysfunction was associated with higher proBNP than normal ventricular function (8,379 vs. 4,778, p = 0.005). No proBNP value was both sensitive and specific for ventricular dysfunction (AUC=0.61).. Among CDH patients, elevated proBNP was associated with high-risk defects, ventricular dysfunction, and mortality. ProBNP shows promise as a biomarker in CDH-associated cardiac dysfunction.

Topics: Echocardiography; Heart Diseases; Hernias, Diaphragmatic, Congenital; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Severity of Illness Index; Ventricular Dysfunction, Left

Severity of lung hypoplasia, pulmonary hypertension (PH) and cardiac dysfunction are major contributors to mortality in congenital diaphragmatic hernia (CDH). Therefore, early assessment and management is important to improve outcome. NT-proBNP is an established cardiac biomarker with only limited data for early postnatal risk assessment in CDH newborns.. To investigate the correlation of NT-proBNP at birth, 6 h, 12 h, 24 h, and 48 h with PH and cardiac dysfunction and the prognostic information of NT-proBNP for the use of ECMO support or mortality.. 44 CDH newborns treated at our institution (December 2014-October 2017) were prospectively enrolled.. Primary clinical endpoint was either need for ECMO or death within the first 48 h (group A). Infants not receiving ECMO support were allocated to group B. Mortality was tested as secondary endpoint.. NT-proBNP levels measured at 6 h, 12 h, 24 h and 48 h postpartum correlated significantly with PH severity following NICU admission and at 24 h, and with severity of cardiac dysfunction at birth, 24 h, 48 h and after 7 days of life. There was no difference in NT-proBNP levels between survivors and non-survivors. NT-proBNP levels were significantly higher in group A at 6 h (p = 0.007), 12 h (p = 0.036), and 24 h (p = 0.007), but not at birth (p = 0.785) or 48 h (p = 0.15) compared to group B.. NT-proBNP analysis in the first 48 h of life may be useful to assess PH and cardiac dysfunction in CDH newborns and to predict the need for ECMO support.

Topics: Electrocardiography; Extracorporeal Membrane Oxygenation; Female; Fetal Blood; Hernias, Diaphragmatic, Congenital; Humans; Hypertension, Pulmonary; Infant; Infant Mortality; Infant, Newborn; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies

Topics: Heart Ventricles; Hernias, Diaphragmatic, Congenital; Humans; Infant; Natriuretic Peptide, Brain; Retrospective Studies; Ventricular Dysfunction, Right

Topics: Heart Ventricles; Hernias, Diaphragmatic, Congenital; Humans; Natriuretic Peptide, Brain; Risk Assessment; Ventricular Function, Right

Prostaglandin E1 (PGE) has been used to maintain ductus arteriosus patency and unload the suprasystemic right ventricle (RV) in neonates with congenital diaphragmatic hernia (CDH) and severe pulmonary hypertension (PH). Here we evaluate the PH response in neonates with CDH and severe PH treated with PGE.. We performed a retrospective chart review of CDH infants treated at our center between 2011 and 2016. In a subset, PGE was initiated for echocardiographic evidence of severe PH, metabolic acidosis, or hypoxemia. To assess PH response, we evaluated laboratory data, including B-type natriuretic peptide (BNP) and echocardiograms before and after PGE treatment. Categorical and continuous data were analyzed with Fisher's exact tests and Mann-Whitney t-tests, respectively.. Fifty-seven infants were treated with PGE a mean 17 ± 2 days. BNP levels declined after 1.4 ± 0.2 days of treatment and again after 5.2 ± 0.6 days. After 6 ± 0.8 days of treatment, echocardiographic estimates of severe PH by tricuspid regurgitation jet velocity, ductus arteriosus direction, and ventricular septum position also improved significantly. Treatment was not associated with postductal hypoxemia or systemic hypoperfusion.. In patients with CDH and severe PH, PGE is well tolerated and associated with improved BNP and echocardiographic indices of PH, suggesting successful unloading of the RV.. Treatment study.. Level III.

Topics: Alprostadil; Echocardiography; Female; Hernias, Diaphragmatic, Congenital; Humans; Hypertension, Pulmonary; Infant, Newborn; Male; Natriuretic Peptide, Brain; Philadelphia; Registries; Retrospective Studies; Treatment Outcome; Vasodilator Agents

B-type natriuretic peptide (BNP), an established biomarker of ventricular pressure overload, is used in the assessment of children with pulmonary hypertension (PH). PH is commonly observed in congenital diaphragmatic hernia (CDH). However, the use of BNP levels to guide treatment in this patient population has not been well defined. In this study, we investigate BNP levels in a large cohort of CDH patients treated at a single institution.. We retrospectively reviewed charts of all CDH patients enrolled in our pulmonary hypoplasia program from 2004-2013. PH was assessed by echocardiography using defined criteria, and patients were further stratified into the following cohorts: no PH, short-term PH (requiring nitric oxide but no additional vasodilatory therapy), long-term PH (requiring continued vasodilatory therapy post-discharge), and ECMO (requiring ECMO therapy).. A total of 132 patients were studied. BNP levels were significantly increased in patients with PH compared to patients with normal pulmonary pressures (P<0.01). BNP levels were not significantly different between the ST-PH, LT-PH, and ECMO cohorts, but all levels in all three cohorts were significantly increased compared to patients who did not develop PH.. Our findings indicate that plasma BNP levels correlate with pulmonary hypertension as well as the requirement for ECMO in CDH patients. Monitoring of serial BNP levels may provide a useful prognostic tool in the management of CDH.

Topics: Extracorporeal Membrane Oxygenation; Female; Hernias, Diaphragmatic, Congenital; Herniorrhaphy; Humans; Hypertension, Pulmonary; Infant, Newborn; Male; Monitoring, Intraoperative; Natriuretic Peptide, Brain; Retrospective Studies; Ventricular Pressure

B-type natriuretic peptide (BNP) has not been evaluated in newborns with congenital diaphragmatic hernia (CDH). We hypothesized that BNP and severity of pulmonary hypertension (PH) would predict clinical outcome in these infants.. We measured BNP levels and assessed severity of PH by echocardiography at 1 d and 1 wk of life. Outcome was classified by status at 56 d (or prior discharge): Good (n = 13) if alive on room air and Poor (n = 14) if expired or receiving respiratory support. We estimated area under the curve (AUC) and 95% confidence interval (CI).. BNP levels were higher at 1 d in newborns with Poor outcome (median 220 pg/ml vs. 55 pg/ml, P < 0.01). At 1 wk, there was no significant difference in BNP level (median 547 pg/ml vs. 364 pg/ml, P = 0.70, for Poor and Good outcomes). At 1 d, BNP level predicted outcome (AUC = 0.91, 95% CI = 0.77-1.0), but this relationship dissipated by 1 wk (AUC = 0.55, 95% CI = 0.31-0.79). Severity of PH did not predict outcome at 1 d (AUC = 0.51, 95% CI = 0.27-0.74), but prediction improved at 1 wk (AUC = 0.80, 95% CI = 0.61-0.99).. BNP is a strong predictor of clinical outcome in newborns with CDH at 1 d of life.

Topics: Area Under Curve; Biomarkers; Female; Hernias, Diaphragmatic, Congenital; Hospital Mortality; Humans; Hypertension, Pulmonary; Infant; Infant Mortality; Infant, Newborn; Male; Natriuretic Peptide, Brain; Perinatal Death; Predictive Value of Tests; Prospective Studies; Risk Factors; ROC Curve; Severity of Illness Index; Time Factors; Treatment Outcome; Ultrasonography

In congenital diaphragmatic hernia (CDH) the severity of pulmonary hypertension (PH) is considered, by several authors, determinant of clinical outcome. Plasmatic N-terminal-pro-B type natriuretic peptide (NT-proBNP) might be useful in diagnosis and management of PH in newborns, although its interest in CDH infants remains to be defined. Early NT-proBNP levels were assessed in CDH infants and correlated with cardiovascular echocardiographic parameters.. 28 newborns, CDH and age-matched controls were enrolled in a prospective study. Clinical condition, NT-proBNP plasmatic levels, echo parameters of PH and biventricular function were assessed at 24 h after delivery as well as survival outcome.. Estimated mean pulmonary pressure and NT-proBNP were significantly higher in CDH than control infants. NT-proBNP significantly correlated with estimated pulmonary artery pressure, right ventricular Tei index, and tricuspid E/A ratio. Additionally, we found that CDH infants with NT-proBNP >11,500 pg/ml experienced a worse prognosis.. We demonstrated that PH is associated with NT-proBNP elevation and diastolic impairment in CDH infants. Early elevations in NT-proBNP levels seem to alert for a subset of CDH infants with worse prognosis.

Topics: Blood Pressure; Case-Control Studies; Echocardiography; Female; Heart; Hernia, Diaphragmatic; Hernias, Diaphragmatic, Congenital; Humans; Hypertension, Pulmonary; Infant, Newborn; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Severity of Illness Index

In congenital diaphragmatic hernia (CDH), pulmonary hypertension increases right ventricle (RV) afterload, which could impair heart function and contribute to poor outcome for most affected infants. Nevertheless, the real significance of vascular pulmonary alterations in perinatal hemodynamics is largely unknown. It is defined that ventricular pressure overload induces increased myocardium gene expression of B-type natriuretic peptide (BNP) and components of the renin-angiotensinogen and endothelin (ET)-1 systems. Our aim was to evaluate perinatal myocardium expression of these genes associated with ventricular pressure overload in a nitrofen-induced CDH rat model.. In the nitrofen-induced CDH rat model, fetuses from dated pregnant Sprague-Dawley rats at 15.5, 17.5, 19.5 and 21.5 days postcoitum as well as newborn pups were assigned to 3 experimental groups: control, nitrofen (exposed to nitrofen, without CDH), and CDH (exposed to nitrofen, with CDH). Myocardial samples collected from the RV and left ventricle (LV) were processed for quantification of messenger RNA (mRNA) of BNP, angiotensinogen, and ET-1.. The perinatal expression of BNP, angiotensinogen, and ET-1 mRNA in the RV and LV of the control group revealed daily changes. During gestation, the expression of BNP and angiotensinogen mRNA underwent significant oscillation compared with control in both nitrofen-exposed fetuses, although we cannot identify significant differences between the nitrofen and CDH groups. After birth, we found a significant increasing expression of all studied genes only in the RV of CDH pups.. Perinatal myocardial quantification of BNP, angiotensinogen, and ET-1 mRNA levels suggests that both nitrofen-exposed and control pups revealed prenatal variations of expression of the studied genes. Moreover, CDH is associated with significant molecular alterations only in the RV after birth.

Topics: Adaptation, Biological; Angiotensinogen; Animals; Base Sequence; Biomarkers; Endothelin-1; Gene Expression; Genetic Markers; Heart Ventricles; Hernia, Diaphragmatic; Hernias, Diaphragmatic, Congenital; Hypertension, Pulmonary; Molecular Sequence Data; Myocardium; Natriuretic Peptide, Brain; Phenyl Ethers; Rats; Rats, Sprague-Dawley; RNA, Messenger