natriuretic-peptide--brain and Infant--Premature--Diseases

To systematically review the diagnostic accuracy of brain natriuretic peptide (BNP) and amino-terminal pro-B-type natriuretic peptide (NT-proBNP) in bronchopulmonary dysplasia (BPD) and BPD-pulmonary hypertension (PH).. PubMed, Embase, the Web of Science, and the Cochrane Library were searched in March 2019. We included studies that evaluated BNP or NT-proBNP in preterm neonates as a marker for predicting BPD, BPD or death, and BPD-PH.. Nine studies evaluating NT-proBNP/BNP were included. The quality of evidence was low, using GRADE criteria. The diagnostic accuracy of NT-proBNP and BNP for diagnosing BPD-PH showed high sensitivity and specificity in infants with BPD. Lower sensitivities and specificities of NT-proBNP and BNP were reported for predicting BPD, BPD or death, compared with that for BPD-PH.. Low quality evidence suggests that NT-proBNP and BNP have adequate diagnostic accuracy for diagnosing and monitoring BPD-PH and may be used to triage patients to receive an echocardiogram.

Topics: Biomarkers; Bronchopulmonary Dysplasia; Humans; Hypertension, Pulmonary; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Natriuretic Peptide, Brain; Peptide Fragments; Reference Standards; ROC Curve; Sensitivity and Specificity

Echocardiogram is the gold standard for the diagnosis of hemodynamically significant patent ductus arteriosus (hsPDA) in preterm neonates. A simple blood assay for brain natriuretic peptide (BNP) or amino-terminal pro-B-type natriuretic peptide (NT-proBNP) may be useful in the diagnosis and management of hsPDA. Our objectives were to determine the diagnostic accuracy of BNP and NT-proBNP for hsPDA in preterm neonates and to explore heterogeneity by analyzing subgroups.. The systematic review was performed as recommended by the Cochrane Diagnostic Test Accuracy Working Group. Electronic databases, conference abstracts, and cross-references were searched. We included studies that evaluated BNP or NT-proBNP (index test) in preterm neonates with suspected hsPDA (participants) in comparison with echocardiogram (reference standard). A bivariate random effects model was used for meta-analysis, and summary receiver operating characteristic curves were generated.. Ten BNP and 11 NT-proBNP studies were included. Studies varied by methodological quality, type of commercial assay, thresholds, age at testing, gestational age, and whether the assay was used to initiate medical or surgical therapy. Sensitivity and specificity for BNP at summary point were 88% and 92%, respectively, and for NT-proBNP they were 90% and 84%, respectively.. The studies evaluating the diagnostic accuracy of BNP and NT-proBNP for hsPDA varied widely by assay characteristics (assay kit and threshold) and patient characteristics (gestational and chronological age); therefore, generalizability between centers is not possible. We recommend that BNP or NT-proBNP assays be locally validated for specific patient population and outcomes, to initiate therapy or follow response to therapy.

Topics: Ductus Arteriosus, Patent; Echocardiography; Female; Gestational Age; Hemodynamics; Humans; Infant, Newborn; Infant, Premature, Diseases; Male; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests

The current uncertainty in relation to treatment of the preterm patent ductus arteriosus reflects limitations to our understanding of the pathophysiology of ductal shunting, most particularly which ducts matter to which babies and when they matter. Doppler ultrasound offers a pragmatic tool with which to assess ductal patency and shunt significance and to allow prediction of spontaneous and therapeutic closure. Biomarkers, such as B-type natriuretic peptide, and clinical signs may have a diagnostic role where ultrasound is not available and also possibly as an adjunct to echocardiography in determining the pathophysiological impact of a ductal shunt in an individual baby.

Topics: Biomarkers; Ductus Arteriosus, Patent; Echocardiography; Female; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Natriuretic Peptide, Brain; Pregnancy

Over recent years, the clinical approach to patency of the ductus arteriosus in the premature neonate has been the subject of intensive reevaluation. What had once been considered inherently obvious is no longer to be taken for granted. In this review we will focus on some of the controversies surrounding various aspects of the pharmacologic treatment regimens for patent ductus arteriosus closure. The pros and cons of prophylactic vs therapeutic indomethacin, of early vs late therapy, of high- vs low-dose indomethacin, of single vs multiple courses of treatment, and of ibuprofen vs indomethacin will be considered. In addition, the possibility that patency of the ductus arteriosus is merely a physiological manifestation of extreme prematurity, and thus does not necessarily need to be therapeutically closed, has become a viable approach in some cases. As such, we will examine echocardiographic and biochemical criteria aimed at determining the clinical and hemodynamic significance of ductal shunting, and thereby of the need to treat. Finally, we speculate on potential therapeutic directions for the future, including individualized treatment regimens and multidrug treatment cocktails for those who fail initial monodrug therapy.

Topics: Acetaminophen; Biomarkers; Dose-Response Relationship, Drug; Ductus Arteriosus, Patent; Echocardiography; Female; Humans; Ibuprofen; Indomethacin; Infant, Newborn; Infant, Premature, Diseases; Male; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Precision Medicine; Pregnancy; Time Factors

Evaluate plasma markers of myocardial function and ischemia [B-type natriuretic peptide] (BNP) and cardiac troponin T (cTnT)] in relationship to echocardiographic indices of left ventricular (LV) function and severity of illness score (SNAPPE-II) in Very-Low-Birth-Weight-Infants (VLBWIs) prospectively.. Serial echocardiography studies, clinical data, BNP and cTnT were obtained in thirty VLBWIs on postnatal days 1, 2, 3 and 7.. BNP increased and cTnT decreased significantly day 1 through 3. BNP was significantly associated with patent ductus arteriosus (PDA), but did not correlate with LV function or cTnT and did not reflect use of inotropic medication. Cardiac troponin T increased with severity of illness, SNAPPE-II, score and was highest in babies receiving inotropic medication; Low cardiac output (CO) was common in the first seventy two hours and correlated negatively with cTnT (p < 0.01). A contractility index, the corrected LV mean velocity of circumferential fiber shortening, (mVcfc) was not related to cTnT. The LV mVcfc was inversely related to LV end systolic wall stress (p < 0.001) in all subgroups, and this index of contractility (mvcfc-ess) did not differ with large caliber PDA or use of inotropic medication.. Cardiac troponin T exclusively rather than a combined biomarker approach may be useful in assessing myocardial injury. Cardiac output was low in sick VLBWIs with myocardial ischemia. Left ventricular contractile state was apparently preserved in significantly ill babies with elevated cTnT. Further research is needed to define the complex relationship between biomarkers and echocardiographic indices.

Topics: Biomarkers; Ductus Arteriosus, Patent; Female; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Logistic Models; Male; Natriuretic Peptide, Brain; Severity of Illness Index; Single-Blind Method; Troponin T; Ultrasonography; Ventricular Dysfunction, Left

Patent ductus arteriosus (PDA) is highly prevalent in pre-term neonates (PTN) and has been recognized as a neonatal co-morbidity. The purpose of this study was to determine if levels of brain (or B-type) natriuretic peptide (BNP), a peptide secreted by ventricular myocytes in response to volume or pressure overload, correlate with the size of the PDA. In a prospective design, 52 PTN (no PDA: n=24; PDA: n=28) were studied after obtaining parental consent. Those with genetic anomalies and congenital heart disease, except for PDA and patent foramen ovale, were excluded. Echocardiographic estimates of the diameters of the PDA (or absence of PDA) were made concurrently with capillary blood collection for BNP assay. BNP levels in samples from PTN without PDA were 23.6 ng/L (median); 13.1 to 32.3 ng/L (IQR); initial samples (between days 3 and 7 of life) with small PDA (n=11), median 66.1 ng/L; 55.5 to 85.3 ng/L (IQR); with moderate PDA (n=6) median 284 ng/L; 204 to 622 ng/L (IQR); and with large PDA (n=11) 2410 ng/L median; 420 to 2770 ng/L (IQR). (p< 0.0001 for ANOVA; groupwise: p<0.05 for both no PDA vs. moderate and large PDA); Trend analysis suggested a strong association of BNP with size of PDA (p<0.001). Of 17 subjects with moderate to large PDA, pre and post-treatment (Ibuprofen; per standard protocol) data were obtained on 12 subjects. Pre-treatment BNP ranged from 111 to 5000 ng/L; post-treatment BNP decreased to 5.0 to 262 ng/L (p = 0.0005). Estimates of decision levels for treatment were made by examining dichotomized groups, i.e., no-to-small vs. moderate-to-large and using receiver-operator characteristic (ROC) curve analysis yielding a value of 123 ng/L. BNP may obviate repeated echocardiography as follow up after treatment, or to monitor future course of respiratory distress secondary to PDA in PTN.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Ductus Arteriosus, Patent; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Natriuretic Peptide, Brain; Point-of-Care Systems; Prospective Studies; Ultrasonography

To determine whether b-type natriuretic peptide (BNP) concentrations can guide treatment of patent ductus arteriosus (PDA) to reduce the number of indomethacin doses without increasing morbidity.. Prospective, randomised, controlled trial.. Single-centre referral neonatal intensive care unit.. Infants with echocardiographic diagnosis of PDA. Infants with congenital heart disease or renal insufficiency were excluded.. BNP measurement and echocardiography were performed in all subjects before and after indomethacin treatment. The investigational group had BNP concentrations measured 12 and 24 h after the first dose (before the 2nd and 3rd doses of indomethacin). Indomethacin dosing was withheld in the BNP-guided group if the 12 or 24 h BNP concentrations were found to be <100 pg/ml.. Number of doses of indomethacin given during the primary course of treatment (three doses every 12 h).. Sixty patients were randomly assigned to control (n = 30) and BNP-guided (n = 30) treatment groups. There was no difference between the groups with respect to gestational age (26(+3) vs 25(+5) weeks, respectively), Apgar scores, delivery method, gender or indomethacin prophylaxis. Median baseline and 48 h BNP concentrations did not differ between the groups (0 h: 500 vs 542 pg/ml; 48 h: 85 vs 126 pg/ml; control and BNP-guided groups, respectively). During primary indomethacin treatment, the BNP-guided group received fewer doses of indomethacin than controls (70 vs 88 doses, p<0.05). The rate of PDA ligation, intestinal perforation and chronic lung disease did not differ between groups.. BNP-guided treatment reduced the number of primary indomethacin doses. There was no increase in PDA persistence or associated morbidity.

Topics: Biomarkers; Cyclooxygenase Inhibitors; Ductus Arteriosus, Patent; Echocardiography; Female; Humans; Indomethacin; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Natriuretic Peptide, Brain; Prospective Studies; Treatment Outcome; Virginia

N-terminal probrain natriuretic peptide (NT-proBNP) is a biomarker of interest in many cardiopulmonary diseases in extremely low birth weight (ELBW) Infants. However, there is a gap in knowledge about the trend of ELBW infant's urinary NT-proBNP during the neonatal period.. To determine the trend of urinary NT-proBNP during the first 4 weeks of life of an ELBW infant.. We analyzed prospectively enrolled 87 ELBW infants. Urinary NT-proBNP to creatinine ratios were measured on days 1 to 7, 14, and 28 of life. We plotted each study point's means to determine the trend of urinary NT-proBNP over the entire neonatal period. Data were analyzed using the Friedman analysis of variance for comparative analysis of study points.. Urinary NT-proBNP/creatinine ratios were significantly elevated on days 1 to 7 (mean 2,452, ± 1,518) than day 14 (mean 747, ± 176), and day 28 (mean 149, ± 54),. Urinary NT-proBNP levels are higher during the first week in ELBW infants with a downward trend during the neonatal period, the lowest values at 4 weeks postnatal age. More studies are required to determine the clinical utility of this trend during and beyond the neonatal period.. · NT-proBNP is a biomarker for monitoring cardiac disease in premature infants.. · The trend of urinary NT-proBNP is unknown in premature infants.. · A trend of urinary NT-proBNP was determined during the first 4 weeks in premature infants..

Topics: Biomarkers; Creatinine; Humans; Infant; Infant, Extremely Low Birth Weight; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies

This pilot study aimed to determine the feasibility of urinary NT-proBNP (NT-proBNP) as a potential noninvasive screening marker for pulmonary hypertension (PH).. A prospective cross-sectional study was conducted. Preterm infants (PI) (birthweight <1500 gm and <30 weeks gestational age (GA)) were enrolled. Serial urinary NT-proBNP measurements and echocardiograms (ECHO) were performed at 28, 32, and 36 weeks.. Thirty-six patients were included in the final analysis (BPD-PH group = 6, BPD group = 20, control = 10). Urinary NT-proBNP levels were higher in the BPD-PH group compared with BPD and control groups at all study intervals. A urine NT-proBNP cutoff level of 2345 pg/ml at 28 weeks of GA had a sensitivity and specificity of 83.3% and 84.2%, respectively, for detection of BPD-PH (AUC 0.816, p = 0.022).. Urinary NT-proBNP measurement is feasible in preterm infants and appears to be a good noninvasive screening tool for PH.

Topics: Adult; Biomarkers; Cross-Sectional Studies; Echocardiography; Female; Humans; Hypertension, Pulmonary; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Male; Maternal Age; Natriuretic Peptide, Brain; Peptide Fragments; Pilot Projects; Prospective Studies; ROC Curve; Sensitivity and Specificity

Early identification of infants at risk for complications from patent ductus arteriosus (PDA) may improve treatment outcomes. The aim of this study was to identify biochemical markers associated with persistence of PDA, and with failure of pharmacological treatment for PDA, in extremely preterm infants.. Infants born at 22-27 weeks' gestation were included in this prospective study. Blood samples were collected on the second day of life. Fourteen biochemical markers associated with factors that may affect PDA closure were analyzed and related to persistent PDA and to the response of pharmacological treatment with ibuprofen.. High levels of B-type natriuretic peptide, interleukin-6, -8, -10, and -12, growth differentiation factor 15 and monocyte chemotactic protein 1 were associated with persistent PDA, as were low levels of platelet-derived growth factor. High levels of erythropoietin were associated with both persistent PDA and failure to close PDA within 24 h of the last dose of ibuprofen.. High levels of inflammatory markers were associated with the persistence of PDA. High levels of erythropoietin were associated with both the persistence of PDA and failure to respond to pharmacological treatment.

Topics: Biomarkers; Chemokine CCL2; Ductus Arteriosus, Patent; Echocardiography; Growth Differentiation Factor 15; Humans; Ibuprofen; Infant, Extremely Premature; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature, Diseases; Inflammation; Interleukin-10; Interleukin-12 Subunit p35; Interleukin-6; Interleukin-8; Natriuretic Peptide, Brain; Platelet-Derived Growth Factor; Prospective Studies; Risk; Sweden

Premature infants with severe bronchopulmonary dysplasia (sBPD) are at risk of pulmonary hypertension (PH). Serum brain natriuretic peptide (BNP) is used to predict disease severity in adult PH. Its diagnostic utility in sBPD-associated PH is unknown.. The aim of this paper was to determine the accuracy of BNP, against echocardiogram (echo), to diagnose PH in infants born <32 weeks' gestation with sBPD.. We conducted a retrospective cohort study of all infants with sBPD with an echo and BNP within a 24-h period, at ≥36 weeks postmenstrual age. PH was defined as: right ventricular pressure >½ systemic blood pressure estimated from tricuspid regurgitant jet or patent ductus arteriosus (PDA) velocity, bidirectional or right-to left-PDA, and/or flat/bowing ventricular septum at end-systole. Receiver-operating characteristic (ROC) curves were constructed to test the diagnostic accuracy of BNP.. Of 128 infants, 68 (53%) had echo evidence of PH. BNP was higher among the infants with PH (median [interquartile range]: 127 pg/mL [39-290] vs. 35 [20-76], p < 0.001). The area under the ROC curve for diagnosing PH using BNP was 0.74 (95% CI 0.66-0.83). At an optimal cutpoint of 130 pg/mL, BNP correctly classified the presence or absence of PH in 70% of the infants (specificity: 92, sensitivity: 50%).. BNP, relative to concurrent echo, demonstrated moderate accuracy for diagnosing PH in this cohort of preterm infants with sBPD. BNP may help rule in PH in this population but has low utility to rule out the disease.

Topics: Biomarkers; Bronchopulmonary Dysplasia; Echocardiography; Gestational Age; Heart Ventricles; Humans; Hypertension, Pulmonary; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Natriuretic Peptide, Brain; Retrospective Studies; ROC Curve

The objective is to examine the correlation between plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and tissue Doppler imaging (TDI) echocardiographic parameters in the first 28 days of life in very-low-birth-weight infants (VLBWI). VLBWI admitted to the Neonatal Intensive Care Unit (NICU) at Hospital Puerta del Mar, Spain, from January 2015 to January 2017 were prospectively enrolled. Weekly determination of plasma NT-proBNP (pg/mL), and echocardiograms were done during the first 28 days of life. 101 preterm infants with a mean GA of 28.85 weeks (± 1.85 SD) and mean birth weight of 1152 g (± 247.4 SD) were included. A total of 483 echocardiograms and 139 NT-proBNP determinations were performed. We found a negative correlation between plasma NT-proBNP levels and diastolic velocities: mitral A' (ρ = - 0.15, p = 0.04), mitral E' (ρ = - 0.17, p = 0.02), tricuspid A' (ρ = - 0.20, p = 0.006), tricuspid E' (ρ = - 0.24, p = 0.0009). In the first 24 h of life, NT-proBNP levels were strongly correlated with mitral A' and E' velocities in patients with no patent ductus arteriosus (PDA) (ρ = - 0.75, p = 0.04). In preterm patients, elevated NT-proBNP levels are related to worse diastolic myocardial function. In the first 24 h, this correlation is much stronger in the absence of PDA.

Topics: Biomarkers; Echocardiography, Doppler; Female; Humans; Infant; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Spain; Ventricular Dysfunction

B-type natriuretic peptide (BNP) has been shown to correlate with pulmonary hypertension (PH) in term neonates with persistent pulmonary hypertension of the newborn or congenital diaphragmatic hernia, and in very preterm infants with bronchopulmonary dysplasia. This study investigated the potential association of BNP and N-terminal-pro-BNP (NTproBNP) and PH within the first 72 hr of life in very preterm infants.. Preterm infants <32 weeks gestational age who received an echocardiogram within the first 72 hr of life were eligible. BNP and NTproBNP were sampled at the time of the echocardiogram. Right ventricular systolic pressure (RVSP) was calculated as a surrogate marker of PH. Simple and multiple linear regression analysis was performed to examine associations and potential confounding factors.. Sixty-one infants were included with a median (IQR) birth weight of 983 g (826-1,167) and a median (IQR) gestational age of 27(2) weeks (26(2) -28(6) ). There was no difference between BNP or NTproBNP levels for infants with or without measurable RVSP. There was no significant correlation of BNP and RVSP in multiple linear regression analysis (regression coefficient -0.0035 (95%CI: -0.020 to 0.013), P = 0.67). Also, NTproBNP and RVSP were not significantly correlated in multiple linear regression analysis (regression coefficient 0.0071 (95%CI: -0.019 to 0.033), P = 0.58).. B-type natriuretic peptides did not correlate with RVSP in the early postnatal period of very preterm infants. Pediatr Pulmonol. 2016;51:820-824. © 2016 Wiley Periodicals, Inc.

Topics: Biomarkers; Blood Pressure; Echocardiography; Female; Gestational Age; Humans; Hypertension, Pulmonary; Infant, Extremely Premature; Infant, Newborn; Infant, Premature, Diseases; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Systole

B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NTproBNP) have been shown to correlate with the size of the patent ductus arteriosus (PDA) in preterm infants. We investigated whether BNP or NTproBNP was more closely correlated with PDA size.. This prospective observational study included preterm infants born <32 weeks' gestation who had an echocardiogram performed within the first four days of life. Blood samples were taken simultaneously for BNP and NTproBNP measurements prior to echocardiographic examination.. Of the 60 infants recruited, 58 had complete data sets. The cohort's mean and standard deviation (SD) gestational age was 27(+3) (2(+2)) weeks, the mean (SD) birthweight was 1032 (315) grams, and 46 (79.3%) infants had a PDA with a mean (SD) diameter of 3.2 (0.9) mm. Median and interquartile range (IQR) BNP levels were 486.5 (219-1316) pg/mL for infants with a PDA and 190 (95.5-514.5) pg/mL for infants without a PDA. Median (IQR) NTproBNP levels were 10 858.5 (6319-42 108) pg/mL for infants with a PDA and 7488 (3363-14 227.5) pg/mL for infants without a PDA. Both BNP (R = 0.35, p = 0.0066) and NTproBNP (R = 0.31, p = 0.018) were significantly correlated with PDA size.. BNP and NTproBNP are similarly useful for assessing PDA size in preterm infants.

Topics: Ductus Arteriosus, Patent; Female; Humans; Infant, Newborn; Infant, Premature, Diseases; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies

Earlier and more accurate identification of a high-risk group of preterm infants that are likely to develop a hemodynamically significant patent ductus arteriosus (hsPDA) would allow specific targeting of early treatment and thus possibly minimize the morbidity and mortality associated with a PDA in extremely low birth weight (ELBW) infants.. To investigate the predictability of B-type natriuretic peptide (BNP) for early targeted treatment of hsPDA in ELBW infants.. 73 ELBW infants that underwent echocardiographic evaluation and plasma BNP measurement after birth were enrolled. 31 infants developed hsPDA (HsPDA group) and 42 infants did not develop hsPDA (nPDA group).. BNP levels of the HsPDA group were significantly higher than those of the nPDA group at 24 h of age (921 [318-2,133] vs. 152 [91-450] pg/ml) but not different at 12 h of age. BNP levels at 24 h of age were significantly correlated with the magnitudes of the ductal shunt but not at 12 h of age. The area under the receiver operator characteristic curve of BNP levels for prediction of hsPDA at 24 h of age was 0.830. At the cutoff BNP levels of 200 and 900 pg/ml at 24 h of age, sensitivity was 83.9 and 54.8% and specificity was 61.9 and 95.2%, respectively.. BNP levels at 24 h of age can be used as a guide for early targeted treatment of hsPDA and avoid the unnecessary use of cyclooxygenase inhibitors in ELBW infants.

Topics: Ductus Arteriosus, Patent; Female; Gestational Age; Humans; Infant, Extremely Low Birth Weight; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Natriuretic Peptide, Brain; Retrospective Studies; ROC Curve; Ultrasonography

In very preterm infants, clinical decision-making, such as closing a patent ductus arteriosus (PDA), may be aided by measuring circulating natriuretic and endothelial pro-peptides.. To investigate the association between perinatal characteristics, PDA echocardiography and plasma concentrations of stable pro-peptides of B-type natriuretic peptide (NT-proBNP), atrial natriuretic peptide (MR-proANP) and endothelin-1 (CT-proET-1).. A prospective, cross-sectional, single-center study was performed in 66 infants who were less than 32 weeks of gestational age. Pro-peptide concentrations were determined at birth and at day 2-3 of life.. Plasma concentrations of all 3 pro-peptides increased on average 2- to 5-fold from birth to day 2-3 of life. NT-proBNP and MR-proANP were closely related at birth and at day 2-3 (Rs 0.902 and 0.897, respectively, p < 0.001), whereas CT-proET-1 was related to NT-proBNP and MR-proANP at birth (Rs 0.478 and 0.460, respectively, p < 0.001) but not at day 2-3. Birth weight was negatively related to all 3 pro-peptides at birth (p < 0.01); however, preeclampsia and compromised placental perfusion were associated with elevated NT-proBNP and MR-proANP concentrations at birth. At day 2-3, MR-proANP and NT-proBNP correlated significantly with the ductal diameter (Rs 0.416 and 0.415, respectively, both p = 0.011), whereas CT-proET-1 correlated with the left atrium/aorta ratio (Rs 0.506, p = 0.027). CT-proET-1 was elevated in infants with treated compared to untreated PDA [median (5-95% range) 388 (272-723) vs. 303 (152-422) pmol/l, p = 0.011], but not NT-proBNP or MR-proANP.. CT-proET-1 is a promising predictor in determining the need for PDA intervention.

Topics: Atrial Natriuretic Factor; Ductus Arteriosus, Patent; Echocardiography; Endothelin-1; Female; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Natriuretic Peptide, Brain; Peptide Fragments; Placenta; Pre-Eclampsia; Pregnancy; Protein Precursors

Although the B-type natriuretic peptide (BNP) levels in the umbilical cord blood (UCB-BNP) and amniotic fluid (AF-BNP) of neonates may be clinically useful for identifying newborns with cardiac dysfunction, the effects of various clinical factors, such as gestational age at birth, small for gestational age (SGA), and neonatal asphyxia, on the UCB-BNP and AF-BNP levels have not been studied extensively.. The present study sought to determine whether the UCB-BNP and AF-BNP levels can predict cardiac dysfunction and hypotension in preterm infants soon after birth and to evaluate the association between BNP and various clinical factors. The UCB-BNP and AF-BNP levels at birth were determined in 320 and 195 neonates, respectively, born to mothers with singleton pregnancies.. The UCB-BNP and AF-BNP levels in infants treated with dopamine were significantly higher than those in infants without dopamine administration (230.1 vs 33.1 pg/mL and 74.4 vs 18.1 pg/mL, respectively). Stepwise multiple regression analyses indicated that gestational age, SGA, asphyxia, and chorioamnionitis were significant independent determinants of the UCB-BNP level. Cut-off values of >90 pg/mL for UCB-BNP and >36 pg/mL for AF-BNP yielded sensitivities of 68% and 93%, respectively, and specificities of 84% and 81%, respectively, for detecting neonates who required dopamine administration after birth.. High UCB-BNP and AF-BNP levels predict neonatal cardiac dysfunction soon after birth.

Topics: Adult; Amniotic Fluid; Chorioamnionitis; Dopamine; Echocardiography; Female; Fetal Blood; Heart Diseases; Humans; Hypotension; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Multivariate Analysis; Natriuretic Peptide, Brain; Pregnancy; Prospective Studies; Regression Analysis; Young Adult

Hemodynamically significant patent ductus arteriosus (hsPDA) is the most common functional cardiovascular disease in preterm infants. The necessity to treat hsPDA can neither be derived solely from clinical nor from echocardiographic criteria.. The aim of this study was to establish non-invasive parameters which can differentiate hsPDA from non-hsPDA.. Urinary protein levels of NT-proBNP, NGAL, and H-FABP were measured and correlated with the necessity of therapy for PDA. In 37 neonates (<1,500 g), urinary protein concentrations were tested on days 0, 2, and 7 by ELISA methodology. Of 37 infants, 12 required therapeutic interventions according to current treatment standards.. Infants receiving an intervention for PDA showed significantly higher levels of pro-BNP, NGAL, and H-FABP at all time points except for NT-proBNP on day 0. Infants requiring a second or third course of ibuprofen had significantly higher levels of H-FABP and NGAL. In all samples, the concentration of the three proteins correlated positively with each other.. The present study shows that measurement of urinary proteins is a powerful and non-invasive method to quantify the effect of PDA on systemic perfusion in preterm infants. Furthermore, NGAL and H-FABP may be used to indicate the necessity of pharmacological or surgical treatment of PDA.

Topics: Acute-Phase Proteins; Birth Weight; Case-Control Studies; Ductus Arteriosus, Patent; Fatty Acid Binding Protein 3; Fatty Acid-Binding Proteins; Female; Hemodynamics; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Lipocalin-2; Lipocalins; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proto-Oncogene Proteins

There is little consensus regarding the use of echocardiography in patent ductus arteriosus (PDA) treatment in preterm infants. The use of troponin T (cTnT) and N-terminal Pro-BNP (NTpBNP) in combination with echocardiography assessment may facilitate the development of a superior predictive model.. To investigate the ability of cTnT, NTpBNP and a PDA scoring system applied at 48 h of life to predict death before discharge and neurodevelopmental outcome at 2 years of age.. Infants <32 weeks and <1500 g were prospectively enrolled. Echocardiography evaluation coupled with cTnT and NTpBNP measurements were done at 48 h. The ductus arteriosus was scored (0-6) according to echocardiography markers of haemodynamic significance. Infants were assessed at 2 years using the Bayley scales and categorised into two groups: Severe Disability/Death before discharge or Normal/Mild Disability.. Sixty infants with a median gestation of 27.7 weeks (26.2-29.4) and a median birth weight of 1.01 kg (0.86-1.22) were followed up to 2 years of age. Plasma cTnT and NTpBNP were higher in the Severe Disability/Death compared to the Normal/Mild Disability group (2.30 μg/l vs 0.19 μg/l, p<0.001; 9209 pmol/l vs 1664 pmol/l, p<0.001, respectively). The severe group had a higher PDA score compared to the mild and normal groups (5 vs 2, p<0.001).. Blood cTnT, NTpBNP and a PDA scoring system at 48 h may facilitate the identification of those infants with a PDA, who are at greatest risk of poor neurodevelopmental outcome at 2 years of age.

Topics: Biomarkers; Birth Weight; Developmental Disabilities; Disability Evaluation; Ductus Arteriosus, Patent; Epidemiologic Methods; Female; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Troponin T; Ultrasonography

Although B-type natriuretic peptide (BNP) concentrations seem to be useful for detecting the presence of patent ductus arteriosus, there is no information about their usefulness for monitoring changes in PDA shunt magnitude.. We performed a retrospective analysis of paired BNP-echocardiogram measurements (obtained from infants (24 to 32 weeks gestation) with clinical suspicion of PDA).. Individual BNP concentrations (n=146, from 88 infants) were significantly related to shunt magnitude at the time of measurement and had good discriminating power for detecting a moderate-or-large shunt (area under receiver-operator characteristic curves (ROC-AUC)=0.85). In total, 36 infants had serial BNP-echocardiogram pairs (n=91) measured during their hospitalization. Changes (either increases or decreases) in BNP concentrations over time had only fair discriminating power (ROC-AUC=0.76) for detecting increases or decreases, respectively, in shunt magnitude.. The high degree of variability in the BNP measurements made them less useful for monitoring changes in magnitude.

Topics: Cardiovascular Agents; Ductus Arteriosus, Patent; Echocardiography; Female; Gestational Age; Humans; Indomethacin; Infant, Extremely Low Birth Weight; Infant, Newborn; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Male; Natriuretic Peptide, Brain; Predictive Value of Tests

NT-proBNP is a reliable index in case of cardiac diseases.. To evaluate the diagnostic usefulness of NT-proBNP as index of the closure of patent ductus arteriosus (PDA) in ELBW.. Considered 73 ELBW (mGA 26+3 weeks; mBW 789 g) with echocardiographical diagnosis of PDA. The closure of the duct was spontaneous in 22%, pharmacological in 49.3% and by surgical ligation in 28.7%. Plasma NT-proBNP levels were measured on day 3 in 35 preterm infants; in 20 of them concentrations of the peptide were assayed on day 3 and on closure of the duct.. On day 3 the median of NT-proBNP levels was 13718 pg/ml (range 1918-70000). Peptide concentrations did not differ between pharmacological treatment and surgical ligation (respectively 13718 and 12342 pg/ml; p = 0.33). Concentrations of NT-proBNP were significantly lower on the closure of the duct (p < 0.0001) compared to concentrations on day 3 (median 12666 at day 3 versus 2443.5 pg/ml at closure), with a decrease of 80.71%.. ELBW showed high variability of NT-proBNP concentrations both on day 3 and on closure of PDA. Although NT-proBNP high levels were indicative of the presence of hsPDA, due to the extreme heterogeneity of the values it was not possible to determine an absolute cut-off concentration of NT-proBNP below which closure of the duct occurred, while a decrease of NT-proBNP > or =80% was a reliable index of PDA closure.

Topics: Biomarkers; Ductus Arteriosus, Patent; Female; Gestational Age; Humans; Ibuprofen; Infant, Extremely Low Birth Weight; Infant, Newborn; Infant, Premature, Diseases; Ligation; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Remission, Spontaneous; Renal Insufficiency; Retrospective Studies

We report a blinded, prospective study of the diagnostic utility of N-terminal pro-brain natriuretic peptide (NTproBNP) measurements for predicting clinically significant patent ductus arteriosus (PDA) and assessing closure.. Plasma NTproBNP was measured during the first week in 100 preterm babies (mean gestation 28.8 +/- 2.9 weeks; mean birth weight 1224 +/- 512 g). Echocardiography was performed between days 5 and 7 by operators, blinded to NTproBNP concentration.. NTproBNP peaked on days 2 and 3, declined by day 7. Twenty babies, later treated for PDA, had significantly higher NTproBNP levels throughout. Areas under receiver operating characteristic (ROC) curves were 0.896, 0.897 and 0.931 on days 2, 3 and 7, respectively (p < 0.0001). A concentration > 2850 pmol/L had diagnostic sensitivity of 90% and specificity of 89% (95% CI: 68, 99; likelihood ratio 8.10). Ductal closure was associated with a fall in mean NTproBNP from 3003 to 839 pmol/L (p < 0.001).. N-terminal pro B-type brain natriuretic peptide (NTproBNP) concentrations peaked and then declined in the first week but remained higher in preterm babies whose PDA required treatment. NTproBNP on day 3 predicted whether a neonatal physician blinded to results would treat a PDA. Fall in plasma NTproBNP indicated closure.

Topics: Biomarkers; Ductus Arteriosus, Patent; Echocardiography; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Reference Values; ROC Curve; Sensitivity and Specificity; Single-Blind Method

A patent ductus arteriosus (PDA) in preterm infants is associated with increased risk of intraventricular haemorrhage (IVH) and death. Cardiac troponin T (cTnT) and N-terminal-pro-B type natriuretic peptide (NTpBNP) are markers of cardiac function and can predict poor outcome in adults.. To determine whether echocardiography and cTnT/NTpBNP levels at 48 h predict death before discharge or severe IVH in preterm infants with a PDA.. Infants born <32 weeks' gestation or <1500 g underwent echocardiographic and cTnT/NTpBNP measurements at 12 and 48 h of life. Infants were divided according to their status at discharge: a closed PDA at 48 h, infants with a PDA at 48 h and IVH III/IV and/or death, and infants with a PDA at 48 h without IVH III/IV or death.. Eighty infants with a median gestation of 28 weeks (IQR 26.1-29.5) and birth weight 1.06 kg (0.8-1.21) were included. At 48 h, infants with a PDA and IVH III/IV and/or death had significantly higher median cTnT/NTpBNP levels compared to infants with a PDA without IVH III/IV and/or death and those with spontaneous PDA closure (NTpBNP 9282, 5121 and 740 pmol/l, respectively, p = 0.008, and cTnT 0.66, 0.25 and 0.13 microg/l, respectively, p = 0.027). There were no differences in echocardiographic parameters of PDA size, left atrial to aortic ratio (LA:Ao), left and right ventricular outputs between the PDA groups.. NTpBNP and cTnT in conjunction with echocardiography may provide a basis for trials of targeted medical treatment in infants with a PDA.

Topics: Biomarkers; Birth Weight; Cerebral Hemorrhage; Ductus Arteriosus, Patent; Epidemiologic Methods; Female; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Troponin T; Ultrasonography

Cardiovascular compromise is increasingly recognized in preterm infants. Currently, echocardiography is the best tool to assess myocardial contractility and guide management. Elevated levels of cardiac troponin T (cTnT) and N-terminal-pro-B type natriuretic peptide (NTpBNP) are associated with poor myocardial contractility and low cardiac output in adults.. To examine the range of cTnT and NTpBNP in preterm infants, to correlate NTpBNP and cTnT with echocardiographic markers of cardiac function and to assess the influence of antenatal and postnatal factors on these biochemical markers.. Plasma concentrations of cTnT and NTpBNP were measured in infants <1500 g at 12 h of age. These were correlated with simultaneous echocardiographic measures of myocardial function and output. Antenatal data, infant demographics and postnatal characteristics were prospectively recorded.. A total of 80 infant had samples taken and echocardiography performed. Their median (interquartile range) cTnT and NTpBNP values were 0.20 microg l(-1) (0.11 to 0.40) and 1273 pmol l(-1) (664 to 2798), respectively. There was a significant inverse correlation between cTnT and echocardiographic markers of myocardial function and stroke volume. NTpBNP significantly correlated with left atrial to aortic root ratio (LA:Ao). There was a weaker but significant negative correlation between NTpBNP and left ventricular (LV) function. The assays were not influenced by gestation, birth weight, gender or mode of delivery.. cTnT and NTpBNP are correlated with echocardiographic measures of cardiac performance in preterm infants. Measurement of levels in the first hours of life may provide useful information regarding myocardial function and volume loading.

Topics: Biomarkers; Cohort Studies; Echocardiography; Female; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Natriuretic Peptide, Brain; Respiratory Distress Syndrome, Newborn; Stroke Volume; Troponin T; Ventricular Dysfunction, Left

Patent ductus arteriosus (PDA) is an important cause of morbidity in extremely preterm infants. As increased plasma brain natriuretic peptide (BNP) is a common feature of adult cardiac disease, we investigated the value of plasma BNP concentration as a predictor of haemodynamically significant PDA in very preterm infants. We studied 18 preterm infants (12 male) of median gestational age 30 weeks (range 24-34), median birth weight 1.46 kg (0.54-2.13) and 11 healthy term controls. Plasma BNP levels were measured by double-antibody radioimmunoassay on days 3, 5 and 7 of life, and an echocardiogram was performed on day 7. Six infants of median gestation 26 weeks (26-30), median birth weight 0.92 kg (0.54-1.04) had PDA proven by echocardiography on day 7. BNP concentrations (pg/ml) on day 3 were significantly higher in these infants than in the remaining twelve [median 2012 (786-2759) versus 42 (7-704), P<0.001]. In four infants PDA was treated successfully (one surgically, three with non-steroidal anti-inflammatory drugs). Two had haemodynamically insignificant closing ducts. In these infants with therapeutic or spontaneous resolution of a PDA, plasma BNP fell to normal values [median after treatment 9 pg/ml (8-27)]. Early measurement of plasma BNP in the first few days of life is a useful method for predicting those preterm infants who may require intervention for PDA.

Topics: Biomarkers; Ductus Arteriosus, Patent; Female; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Natriuretic Peptide, Brain

Topics: Biomarkers; Ductus Arteriosus, Patent; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Natriuretic Peptide, Brain