Péptido natriurético cerebral tipo B como marcador de sobrecarga hemodinámica del conducto arterioso permeable en el recién nacido prematuro / B-type brain natriuretic peptide as marker of hemodynamic overload of the patent ductus arteriosus in the preterm infant

Resumen Introducción: El ecocardiograma es el método de referencia para el diagnóstico del conducto arterioso permeable (CAP) hemodinámicamente significativo (CAP-hs) del recién nacido prematuro (RNP). El péptido natriurético tipo B (BNP) puede ser útil en el diagnóstico y el manejo del CAP-hs. Objetivo: Evaluar la utilidad del BNP como marcador de sobrecarga hemodinámica del conducto arterioso permeable en el RNP con edad gestacional < 32 semanas o peso < 1500 gramos, e identificar el mejor punto de corte para los valores de BNP que mejor prediga un CAP con repercusión hemodinámica que requiera tratamiento farmacológico o quirúrgico. Método: Estudio retrospectivo, observacional y descriptivo de RNP < 32 semanas de gestación o peso < 1500 gramos en los que se realizó ecocardiograma y determinación del BNP. Análisis de muestra global y por subgrupos, en función del CAP-hs. Resultados: Se analizaron 29 pacientes. Se encontró una correlación significativa entre la relación CAP/peso y los valores del BNP (prueba de Spearman: 0.71; intervalo de confianza del 95%: 0.45-0.87; p < 0.001). El mejor punto de corte del BNP para predecir CAP-hs fue 486.5 pg/ml, con una sensibilidad del 81% y una especificidad del 92% (p < 0.001). Conclusión: El punto de corte del BNP identificado en el presente estudio se correlacionó con la presencia de CAP-hs.

Abstract Introduction: The echocardiogram is the gold standard, in the diagnosis of the hemodynamically significant patent ductus arteriosus (hs-PDA) of the premature newborn (PNB). Type B natriuretic peptide (BNP) may be useful in the diagnosis and management of CAP-hs. Objective: To assess the utility of BNP as a marker of hemodynamic overload of the patent ductus arteriosus in newborns with gestational age < 32 weeks or weight < 1500 grams, and to identify the best cut-off point for BNP levels that would best predict a PDA with hemodynamic impact requiring pharmacological and/or surgical treatment. Methods: Retrospective, observational and descriptive study of PNB < 32 weeks gestation or weight < 1500 grams, in which echocardiogram and BNP determination was performed. Analysis of the global sample and by subgroups, depending on the hs-PDA status was performed. Results: A total of 29 patients were analyzed. A significant correlation was found between the PDA/weight ratio and BNP levels (Spearman: 0.71; 95% confidence interval: 0.45-0.87; p < 0.001). The best BNP cut-off point to predict CAP-hs was 486.5 pg/ml with a sensitivity of 81% and specificity of 92% (p < 0.001). Conclusion: The BNP cut-off point identified in the present study was correlated with the presence of CAP-hs.

Does high dose intravenous acetaminophen affect liver function for PDA closure in premature neonate?

OBJECTIVES: The aim of this study was to collect consistent data on the efficacy and safety and evaluation hepatotoxicity of intravenous acetaminophen for the treatment of PDA in preterm infants. METHODS: This is an observational longitudinal prospective study on 46 preterm infants with PDA who treated with high dose of acetaminophen and evaluated with echocardiography and serum liver enzymes at Hafez and Zeinabiyeh hospitals from January 2016 to December 2019. RESULT: Forty-six preterm infants with PDA treated with intravenous acetaminophen. Rate of closure of PDA was 82.6. There was no significant difference after treatment regarding AST, ALT, Albumin, total and direct bilirubin (P value > 0.05) and no adverse side effects were observed in association with intravenous acetaminophen. CONCLUSION: High dose of acetaminophen is not more effective than that with standard doses although without hepatotoxic side effect for PDA closure.

[B-type brain natriuretic peptide as marker of hemodynamic overload of the patent ductus arteriosus in the preterm infant]. / Péptido natriurético cerebral tipo B como marcador de sobrecarga hemodinámica del conducto arterioso permeable en el recién nacido prematuro.

Introducción: El ecocardiograma es el método de referencia para el diagnóstico del conducto arterioso permeable (CAP) hemodinámicamente significativo (CAP-hs) del recién nacido prematuro (RNP). El péptido natriurético tipo B (BNP) puede ser útil en el diagnóstico y el manejo del CAP-hs. Objetivo: Evaluar la utilidad del BNP como marcador de sobrecarga hemodinámica del conducto arterioso permeable en el RNP con edad gestacional < 32 semanas o peso < 1500 gramos, e identificar el mejor punto de corte para los valores de BNP que mejor prediga un CAP con repercusión hemodinámica que requiera tratamiento farmacológico o quirúrgico. Método: Estudio retrospectivo, observacional y descriptivo de RNP < 32 semanas de gestación o peso < 1500 gramos en los que se realizó ecocardiograma y determinación del BNP. Análisis de muestra global y por subgrupos, en función del CAP-hs. Resultados: Se analizaron 29 pacientes. Se encontró una correlación significativa entre la relación CAP/peso y los valores del BNP (prueba de Spearman: 0.71; intervalo de confianza del 95%: 0.45-0.87; p < 0.001). El mejor punto de corte del BNP para predecir CAP-hs fue 486.5 pg/ml, con una sensibilidad del 81% y una especificidad del 92% (p < 0.001). Conclusión: El punto de corte del BNP identificado en el presente estudio se correlacionó con la presencia de CAP-hs.

Cardiovascular biomarkers in the evaluation of patent ductus arteriosus in very preterm neonates: A cohort study.

BACKGROUND: The evaluation of the patent ductus arteriosus (PDA) in the very premature neonate is a challenge. Echocardiography provides an interpretation of the hemodynamic condition. It is however, only a snapshot. Biomarkers may represent a physiological response to the hemodynamic alterations brought on by the PDA and may add to the identification of the clinical significant PDA. AIM: To investigate the association between mid regional proadrenomodulin (MR-proADM), N-terminal pro b-type natriuretic peptide (NT-proBNP), mid regional pro-atrial natriuretic peptide (MR-proANP), C-terminal pro endothelin-1 (CT-proET1) and copeptin and echocardiographic measures of PDA. STUDY DESIGN: Cohort study with echocardiography performed on day 3 and 6. Blood samples from day 3. SUBJECT: 139 consecutive neonates born at a gestational age <32 weeks. OUTCOME MEASURES: The main outcomes were presence of a PDA day 3 and 6, PDA diameter, left atrium to aorta ratio (LA:Ao-ratio), and descending aorta diastolic flow (DADF). RESULTS: Adjusted plasma levels of all investigated biomarkers, except CT-proET1, were found to be associated with both PDA diameter and LA:Ao-ratio, and also the presence of a large PDA. CT-proET1 and copeptin was found to be associated with abnormal DADF. Using pre-specified cut-off values NT-proBNP and MR-proANP day 3 seemed to be of value in identifying a large PDA day 3 and 6 in very preterm neonates. CONCLUSION: Among the investigated biomarkers NT-proBNP and MR-proANP performed best in relation to echocardiographic markers of PDA severity in very preterm neonates.

Proteomics analysis of plasma protein changes in patent ductus arteriosus patients.

OBJECTIVE: Patent ductus arteriosus (PDA) is a congenital heart defect with an unclear etiology that occurs commonly among newborns. Adequately understanding the molecular pathogenesis of PDA can contribute to improved treatment and prevention. Plasma proteins may provide evidence to explore the molecular mechanisms of abnormal cardiac development. METHODS: Isobaric tags for relative and absolute quantitation (iTRAQ) proteomics technology was used to measure different plasma proteins in PDA patients (n = 4) and controls (n = 4). The candidate protein was validated by ELISA and Western blot (WB) assays in a larger sample. Validation of the location and expression of this protein was performed in mouse heart sections. RESULTS: There were three downregulated proteins and eight upregulated proteins identified in the iTRAQ proteomics data. Among these, protein disulfide-isomerase A6 (PDIA6) was further analyzed for validation. The plasma PDIA6 concentrations (3.2 ± 0.7 ng/ml) in PDA patients were significantly lower than those in normal controls (5.8 ± 1.2 ng/ml). In addition, a WB assay also supported these results. PDIA6 was widely expressed in mouse heart outflow tract on embryonic day 14.5. CONCLUSION: Plasma proteomics profiles suggested novel candidate molecular markers for PDA. The findings may allow development of a new strategy to investigate the mechanism and etiology of PDA.

Mature and immature platelets during the first week after birth and incidence of patent ductus arteriosus.

BACKGROUND: Thrombocytopenia is a risk factor for patent ductus arteriosus. Immature and mature platelets exhibit distinct haemostatic properties; however, whether platelet maturity plays a role in postnatal, ductus arteriosus closure is unknown. METHODS: In this observational study, counts of immature and mature platelets (=total platelet count - immature platelet count) were assessed on days 1, 3, and 7 of life in very low birth weight infants (<1500 g birth weight). We performed echocardiographic screening for haemodynamically significant patent ductus arteriosus on day 7. RESULTS: Counts of mature platelets did not differ on day 1 in infants with (n = 24) and without (n = 45) haemodynamically significant patent ductus arteriosus, while infants with significant patent ductus arteriosus exhibited lower counts of mature platelet on postnatal days 3 and 7. Relative counts of immature platelets (fraction, in %) were higher in infants with patent ductus arteriosus on day 7 but not on days 1 and 3. Receiver operating characteristic curve analysis unraveled associations between both lower mature platelet counts and higher immature platelet fraction (percentage) values on days 3 and 7, with haemodynamically significant ductus arteriosus. Logistic regression analysis revealed that mature platelet counts, but not immature platelet fraction values, were independent predictors of haemodynamically significant patent ductus arteriosus. CONCLUSION: During the first week of postnatal life, lower counts of mature platelets and higher immature platelet fraction values are associated with haemodynamically significant patent ductus arteriosus. Lower counts of mature platelet were found to be independent predictors of haemodynamically significant patent ductus arteriosus.

N-terminal pro-brain natriuretic peptide used for screening hemodynamically significant patent ductus arteriosus in very low birth weight infants: How and when?

BACKGROUND: N-terminal pro-B-type natriuretic peptide (NTproBNP) appears to be a useful tool for diagnosing hemodynamically significant patent ductus arteriosus (hsPDA) in preterm infants. However, a consensus for its application has not been reached. OBJECTIVE: The present study aims to evaluate the role of NTproBNP in predicting hsPDA in preterm infants, and explore the optimal cutoff value and testing-time. METHODS: A prospective blind study of 120 preterm infants with birth weights of < 1,500 g was conducted at the NICU of Peking University Shenzhen Hospital. Blood samples were successively collected on the first three days after birth for NTproBNP analysis. Echocardiographies were performed on day three of life to confirm the status of the ductus arteriosus. A receiver operating characteristic curve (ROC) analysis was performed to determine the ability of NTproBNP to recognize hsPDA. RESULTS: NTproBNP was significantly higher in infants with hsPDA, than in infants in the control group, on both day two (P < 0.001) and day three (P < 0.001). On day two, a NTproBNP cutoff value of 3,689.0 pmol/L offered an optimal predictive value for hsPDA, while on day three, the optimal cut-off value for hsPDA was 2,331.5 pmol/L. The investigators proposes day three of life (48-72 hours) as the optimal testing time. CONCLUSION: The NTproBNP biomarker during the early neonatal period can be a useful tool for screening and assessing hsPDA in premature infants, especially on day three of life.

Plasma B-type natriuretic peptide cannot predict treatment response to ibuprofen in preterm infants with patent ductus arteriosus.

Plasma B-type natriuretic peptide (BNP) is a useful marker for diagnosis of hemodynamically significant PDA (hsPDA) and serial BNP measurement is also valuable for monitoring treatment response. This retrospective study was performed to evaluate whether plasma BNP level can predict treatment response to ibuprofen in preterm infants born at <30 weeks of gestation with hsPDA. Plasma BNP was measured before (baseline) and 12 to 24 h after (post-treatment) completion of the first (IBU1) and second (IBU2) course of ibuprofen. We compared the BNP levels of responders (closed or insignificant PDA) with those of non-responders (hsPDA requiring further pharmacologic or surgical closure) to each course of ibuprofen. The treatment response rates for IBU1 (n = 92) and IBU2 (n = 19) were 74% and 26%, respectively. In IBU1, non-responders had lower gestational age and birth weight than responders (both, P = 0.004), while in IBU2, non-responders had lower birth weight (P = 0.014) and platelet counts (P = 0.005) than responders; however, baseline BNP levels did not differ significantly between responders and non-responders in either IBU1 (median 1,434 vs. 1,750 pg/mL) or IBU2 (415 vs. 596 pg/mL). Post-treatment BNP was a useful marker for monitoring treatment efficacy of IBU1 and IBU2 for hsPDA with a cut-off value of 331 pg/mL (P < 0.001) and 423 pg/mL(P < 0.010), respectively. We did not identify a cut-off baseline BNP level that could predict treatment response to ibuprofen in preterm infants with hsPDA.

Hemolytic specimens in complete blood cell count: Red cell parameters could be revised by plasma free hemoglobin.

INTRODUCTION: Hemolysis is the main cause of unqualified clinical samples. In this study, we established a method for detecting and evaluating hemolysis in whole blood test. We used a mathematical formula for correcting the influence of hemolysis on complete blood cell count (CBC) so as to avoid re-venipuncture and obtain more accurate parameters of red blood cell detection, reduce the burden of patients, and improve the efficiency of diagnosis and treatment. METHODS: Hemolytic samples were selected and then corrected using the new formula. Plasma free hemoglobin (fHB) was used as the criterion to determine the degree of hemolysis; the uncertainty of measurement is acceptable as the limit value of deviation between the measured value and the revised value. Hemolysis simulation analysis in vitro and continuous monitoring of clinical patients were used to verify the correction effect. RESULTS: A total of 83 clinical samples with hemolysis were collected and analyzed; fHB 1.4 g/L was selected as the unacceptable value for clinical hemolysis detection. In hemolytic samples, the red blood cell parameters corrected by formula are significantly different from those uncorrected and had a good consistency with those before hemolysis. CONCLUSION: The results show that the hemolysis phenomenon of CBC has a significant impact on routine blood testing. By using the new formula, the influence of hemolysis on erythrocyte and related parameters can be quickly and easily corrected, thus avoiding venipuncture again for re-examination, reducing diagnostic errors, and saving medical resources.

Is high platelet distribution width in the first hours of life can predict hemodynamically significant patent ductus arteriosus in preterm newborns?

Aim: To determine whether there is any association between platelet indices within the first hours of life and hemodynamically significant patent ductus arteriosus (hsPDA) in preterm newborns.Patient and methods: A total of 100 preterm infants, gestational age <32 weeks and birth weight <1500 g were analyzed in the study. Complete blood counts obtained within the first 6 hours of life were evaluated for platelet parameters and compared for patent ductus arteriosus (PDA) status.Results: We included 50 infants with hsPDA and 50 controls. Mean gestational week of patients were 28.8 ± 2.4 weeks and mean birth weight of the patients were 1237.5 ± 406 g. Platelet distribution width (PDW) is higher in PDA group compared with the control group (p = .023). The cutoff value of PDW is 11.45 fL for hsPDA with 65% sensitivity and 66% specificity. The other blood parameters including platelet count, platelet mass, and mean platelet volume (MPV) were no statistically different between the two groups. Also, there was no association with the platelet count and the response to the medical therapy.Conclusions: There is no association between hsPDA and the platelet count, platelet mass or MPV in the first day of life. We determined that hsPDA patency was significantly associated with a higher first day PDW level, which is a more specific indicator of platelet activation than other platelet parameters.

Is the First Postnatal Platelet Mass as an Indicator of Patent Ductus Arteriosus?

BACKGROUND: The aim of this study is to evaluate whether there is an association between the platelet mass and patent ductus arteriosus (PDA) closure in premature newborns. METHODS: Preterm infants (gestational age ≤33 weeks) with hemodynamically significant PDA (group 1, n = 178) and a control group of preterm infants without PDA (group 2, n = 211) were retrospectively evaluated between August 1, 2013 and July 30, 2015 in the neonatal intensive care unit (NICU). Platelet counts and platelet indices including mean platelet volume (MPV), and platelet mass (platelet count x mean platelet volume) in the first 24 hours of life, demographic findings and morbidities were recorded. RESULTS: No differences were observed in demographic findings between the study groups in terms of birth weight, gestational age, gender and maternal risk factors. The mean platelet count in the first postnatal hemogram in group 1 and group 2 were 189.43 ± 72.14 (X103 /mm3) and 206.86 ± 70.11(X103/mm3), respectively (P < 0.05). The MPV were similar in both groups (P > 0.05). Platelet mass values were 1443.70 ± 572.40 fL/nL in Group 1 and 1669.49 ± 1200.42 fL/nL in group 2. There was a statistically significant difference in platelet mass values between the two groups (P = 0.011). Multivariable analysis including presence of thrombocytopenia, MPV and platelet mass showed that hemodynamically significant PDA was not independently associated with platelet count <150 000 (OR = 1.001, 95% CI 0.980-1.023; P = 0.921), MPV (OR = 0.967, 95% CI 0.587-1.596; P = 0.897) or platelet mass (OR = 0.999, 95% CI 0.997-1.002; P = 0.681). The optimal cut-off value of platelet mass for patients with PDA was ≤1530.8 fL/nL (area under the curve [AUC]: 0.580), with sensitivity of 58% and specificity of 56.2% (P = 0.008). CONCLUSION: Our data suggest that platelet count, MPV, and platelet mass do not contribute to closure of PDA in premature newborns.

Predicting the serum digoxin concentrations of infants in the neonatal intensive care unit through an artificial neural network.

BACKGROUND: Given its narrow therapeutic range, digoxin's pharmacokinetic parameters in infants are difficult to predict due to variation in birth weight and gestational age, especially for critically ill newborns. There is limited evidence to support the safety and dosage requirements of digoxin, let alone to predict its concentrations in infants. This study aimed to compare the concentrations of digoxin predicted by traditional regression modeling and artificial neural network (ANN) modeling for newborn infants given digoxin for clinically significant patent ductus arteriosus (PDA). METHODS: A retrospective chart review was conducted to obtain data on digoxin use for clinically significant PDA in a neonatal intensive care unit. Newborn infants who were given digoxin and had digoxin concentration(s) within the acceptable range were identified as subjects in the training model and validation datasets, accordingly. Their demographics, disease, and medication information, which were potentially associated with heart failure, were used for model training and analysis of digoxin concentration prediction. The models were generated using backward standard multivariable linear regressions (MLRs) and a standard backpropagation algorithm of ANN, respectively. The common goodness-of-fit estimates, receiver operating characteristic curves, and classification of sensitivity and specificity of the toxic concentrations in the validation dataset obtained from MLR or ANN models were compared to identify the final better predictive model. RESULTS: Given the weakness of correlations between actual observed digoxin concentrations and pre-specified variables in newborn infants, the performance of all ANN models was better than that of MLR models for digoxin concentration prediction. In particular, the nine-parameter ANN model has better forecasting accuracy and differentiation ability for toxic concentrations. CONCLUSION: The nine-parameter ANN model is the best alternative than the other models to predict serum digoxin concentrations whenever therapeutic drug monitoring is not available. Further cross-validations using diverse samples from different hospitals for newborn infants are needed.

Early prediction of spontaneous Patent Ductus Arteriosus (PDA) closure and PDA-associated outcomes: a prospective cohort investigation.

BACKGROUND: Patent ductus arteriosus (PDA), the most commonly diagnosed cardiovascular condition in preterm infants, is associated with increased mortality and harmful long-term outcomes (chronic lung disease, neurodevelopmental delay). Although pharmacologic and/or interventional treatments to close PDA likely benefit some infants, widespread routine treatment of all preterm infants with PDA may not improve outcomes. Most PDAs close spontaneously by 44-weeks postmenstrual age; treatment is increasingly controversial, varying markedly between institutions and providers. Because treatment detriments may outweigh benefits, especially in infants destined for early, spontaneous PDA closure, the relevant unanswered clinical question is not whether to treat all preterm infants with PDA, but whom to treat (and when). Clinicians cannot currently predict in the first month which infants are at highest risk for persistent PDA, nor which combination of clinical risk factors, echocardiographic measurements, and biomarkers best predict PDA-associated harm. METHODS: Prospective cohort of untreated infants with PDA (n=450) will be used to predict spontaneous ductal closure timing. Clinical measures, serum (brain natriuretic peptide, N-terminal pro-brain natriuretic peptide) and urine (neutrophil gelatinase-associated lipocalin, heart-type fatty acid-binding protein) biomarkers, and echocardiographic variables collected during each of first 4 postnatal weeks will be analyzed to identify those associated with long-term impairment. Myocardial deformation imaging and tissue Doppler imaging, innovative echocardiographic techniques, will facilitate quantitative evaluation of myocardial performance. Aim1 will estimate probability of spontaneous PDA closure and predict timing of ductal closure using echocardiographic, biomarker, and clinical predictors. Aim2 will specify which echocardiographic predictors and biomarkers are associated with mortality and respiratory illness severity at 36-weeks postmenstrual age. Aim3 will identify which echocardiographic predictors and biomarkers are associated with 22 to 26-month neurodevelopmental delay. Models will be validated in a separate cohort of infants (n=225) enrolled subsequent to primary study cohort. DISCUSSION: The current study will make significant contributions to scientific knowledge and effective PDA management. Study results will reduce unnecessary and harmful overtreatment of infants with a high probability of early spontaneous PDA closure and facilitate development of outcomes-focused trials to examine effectiveness of PDA closure in "high-risk" infants most likely to receive benefit. TRIAL REGISTRATION: ClinicalTrials.gov NCT03782610. Registered 20 December 2018.

Useful Platelet Indices for the Diagnosis and Follow-Up of Patent Ductus Arteriosus.

OBJECTIVE: The aim of this study was to assess the utility of early postnatal platelet indices in the prediction of hemodynamically significant patent ductus arteriosus (hsPDA) and its response to pharmacological treatment in preterm infants. STUDY DESIGN: The medical records of 971 infants with gestational age < 30 weeks and birth weight < 1,500 g were analyzed retrospectively. Infants with hsPDA comprised the study group and those without hsPDA comprised the control group. Complete blood count results were recorded, and red cell distribution width-to-platelet ratio (RPR) and platelet mass were calculated. RESULTS: A total of 481 infants, 169 in the hsPDA group and 312 in the control group, were included. In terms of platelet indices, the hsPDA group showed significantly lower mean platelet volume (MPV) and platelet mass, whereas RPR was significantly higher (p < 0.05, respectively). Multiple logistic regression analysis showed that RDS (relative ratio [RR]: 2.39; 95% confidence interval [CI]: 1.45-3.93; p < 0.001), MPV < 7.85 (RR: 3.71; 95% CI: 2.29-6.01; p < 0.001), and RPR > 0.070 (RR: 5.33; 95% CI: 3.28-8.65; p < 0.001) were independent risk factors for hsPDA. CONCLUSION: Low MPV and platelet mass and high RPR in the first hours of life are risk factors for hsPDA and hsPDA refractive to pharmacological treatment with ibuprofen in preterm infants.

Exploration of potential biochemical markers for persistence of patent ductus arteriosus in preterm infants at 22-27 weeks' gestation.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Can lactate levels be used as a marker of patent ductus arteriosus in preterm babies?

OBJECTIVE: Serum lactate levels provide information on metabolic capacity at the cellular level. In addition, lactate reflects tissue perfusion and oxygenation status. The aim of this study was to determine the usefulness of high lactate levels as a marker in hemodynamically significant patent ductus arteriosus (hsPDA), which may lead to tissue perfusion defects. METHODS: Preterm infants with gestational age ≤32 weeks and birthweight ≤1500 g were included. Lactate levels were determined at postnatal 48-72 hours before echocardiographic evaluation. Eligible infants were divided into two groups as infants with and without hsPDA. Cut-off values for lactate were taken as lactate >4 mmol/L, identified as a high lactate level. Infants were also divided into two groups according to lactate levels as group I: lactate levels >4 mmol/L and group II: lactate levels ≤4 mmol/L. Haemodynamic PDA and lactate levels were compared. RESULTS: A total of 119 patients with gestational age ≤32 weeks and birthweight ≤1500 g were included in the study. Fifty patients had echocardiographic hsPDA and 69 patients had no PDA. Twelve (24%) of the patients with hsPDA and 22 (31.9%) of the non-hsPDA patients had a lactate level of 4 mmol/L (P = 0.392). There was no correlation between hsPDA presence and lactate levels (P = 0.35). CONCLUSION: High lactate levels are multifactorial and usually indicate impairment of tissue perfusion. There are a number of factors that can lead to impaired tissue perfusion in preterm infants. For the first time in this study, it was shown that lactate levels did not significantly increase in the presence of hemodynamically significant PDA. This may be due to the fact that peripheral tissue perfusion in the presence of hemodynamic PDA does not deteriorate enough to cause an increase in anaerobic metabolism.

High-sensitivity troponin T in preterm infants with a hemodynamically significant patent ductus arteriosus.

OBJECTIVE: To investigate if a hemodynamically significant patent ductus arteriosus (hsPDA) leads to elevated high-sensitivity troponin T (hsTnT) and NTproBNP levels in serum. STUDY DESIGN: Infants <34 weeks and <1500 g were prospectively enrolled, except those with major congenital or chromosomal anomalies. An echocardiogram (ECHO) was performed and hsTnT and NTproBNP were measured within 5 days of life and repeated after treatment of hsPDA. Clinical, ECHO, and hsTnT data were analyzed using Student t-test, two proportion z-test, and regression analysis. RESULTS: Seventy infants were enrolled. Infants in the hsPDA group had lower gestation and birth weight. Mean hsTnT and NTproBNP levels in the hsPDA group were higher compared to the group without an hsPDA, with levels being 251.54 vs 161.6 pg/ml, p < 0.01 for hsTnT and 18181.02 vs 3149.23 pg/ml, p < 0.001 for NTproBNP. CONCLUSION: HsPDA leads to increased hsTnT and NTproBNP levels in preterm infants without affecting cardiac function.

A promising, novel index in the diagnosis and follow-up of patent ductus arteriosus: Red cell distribution width-to-platelet ratio.

BACKGROUND: The role of red cell distribution width-to-platelet ratio (RPR) has not previously been mentioned in reports on patent ductus arteriosus (PDA). Our objective was to evaluate whether RPR would have a role in the diagnosis and/or prediction of pharmacological closure of PDA. METHODS: Preterm infants' gestational age ≤30 weeks and ≤1500 g who were given first ibuprofen treatment in the first week of life for hemodynamically significant PDA (hsPDA) were included in the study. The patients were matched for gestational age, birthweight, and sex. Patients were subdivided into two groups based on the response to medical treatment (open and closed PDA). Hemogram parameters were recorded before and after medical therapy. Groups were compared with regard to demographic and clinical characteristics and for three sequential hematological parameters. RPR was calculated. Patients with sepsis, anemia, perinatal asphyxia, and congenital/chromosomal anomaly were not included in the study. RESULTS: A total of 112 infants had medically treated hsPDA. Of those, ductus closed in 70 neonates (closed PDA). A total of 96 infants constituted the control group. Mean gestational age and birthweight of the patients were 28.9 ± 2.4 weeks and 1207 ± 372 g. While RPR was significantly increased, PCT was lower in both hsPDA and open PDA groups (P < 0.05 and P < 0.05, respectively). In multivariate analysis, high RPR (OR 3.3, 95% CI 1.438-5.872, P < 0.05) and RDS (OR 2.9, 95% CI 1.903-4.811, P < 0.01) were detected as independent risk factors for hsPDA. CONCLUSION: Red cell distribution width-to-platelet ratio and PCT may be promising supportive tools for the diagnosis and prediction of pharmacotherapy success.

Early NT-proBNP levels as a screening tool for the detection of hemodynamically significant patent ductus arteriosus during the first week of life in very low birth weight infants.

OBJECTIVE: To assess whether early NT-ProBNP can identify the need for echocardiographic assessment of hemodynamically significant patent ductus arteriosus (HsPDA) in preterm infants. STUDY DESIGN: Prospective observational study of infants with a gestational age ≤32 weeks. Echocardiographic assessment and NT-proBNP measurement were performed at 48-96 h. ROC curves were generated to assess optimal cutoffs to detect HsPDA and predict the need for treatment. RESULTS: Eighty-five patients were included. HsPDA was present in 28 infants (37.6%), and 22 (25.8%) received treatment. The optimal NT-proBNP cutoff for the detection of HsPDA was 5099 pg/mL (sensitivity 94%, specificity 82%, area under the curve 0.941, P < 0.001). Only 1 child with NT-proBNP levels <5099 pg/mL was ultimately treated for PDA. NT-proBNP screening could have avoided 45 of 85 routine echocardiograms (53%). CONCLUSION: NT-proBNP screening at 48-96 h of life may identify preterm infants at low risk for HsPDA, improving PDA management.

Paracetamol Serum Concentrations in Neonates Treated Enterally for Ductal Closure: A Pilot Study.

We determined serum paracetamol concentrations 4 hours after the eighth dose in infants treated enterally for ductal closure. Serum paracetamol concentrations correlated (P = .0026) with ductal response. No patent ductus arteriosus in a baby with paracetamol levels <20 mg/L closed in response to treatment. Paracetamol levels also correlated (P = .046) with postnatal age.