Relationship Between Postnatal Pulmonary Arterial Pressure and Altered Diastolic Function in Neonates with Down Syndrome.

OBJECTIVE: To assess the influence of diastolic dysfunction on the evolution of pulmonary hypertension in neonates with Down Syndrome over the early newborn period. STUDY DESIGN: This was a prospective observational cohort study. Echocardiography was performed three times over the first week of life in both Down syndrome and control cohorts. Measurements of pulmonary arterial pressure in addition to left ventricular (LV) and right ventricular systolic and diastolic function were collected. RESULTS: Seventy babies with Down syndrome and 60 control infants were enrolled. Forty-eight of the infants with Down syndrome (69%) were born with congenital heart disease (CHD). Echocardiography surrogates of pulmonary hypertension and myocardial function remained significantly impaired in the Down syndrome group in comparison with control infants (all P < .01). In the Down syndrome group, LV early diastolic strain rate was independently associated with measures of pulmonary hypertension while controlling for gestational age, cesarean delivery, and the presence of CHD (P < .01). CONCLUSIONS: Intrinsic LV diastolic impairment is directly associated with higher indices of pulmonary hypertension in infants with Down syndrome and may be a contributing factor to its evolution.

Cardiac Function and Ventricular Interactions in Persistent Pulmonary Hypertension of the Newborn.

OBJECTIVES: The aim of this study was to use a comprehensive imaging protocol to identify echocardiographic correlations of right and left ventricular size, function, and hemodynamics in neonates with persistent pulmonary hypertension of newborn and describe their relationship with key clinical variables. DESIGN: Retrospective case-control echocardiography-based study of persistent pulmonary hypertension of newborn. SETTING: A tertiary neonatal ICU in Canada. PATIENTS: Forty-nine neonates (gestational age ≥ 35 wk old) diagnosed with persistent pulmonary hypertension of newborn within first 3 days after birth and 50 age-matched controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The echocardiographic measurements comprised of right ventricular and left ventricular functional markers, including tricuspid annular plane systolic excursion, fractional area change, tissue Doppler imaging, and deformation imaging. Sample size was based on detecting an intergroup difference of 10% in tricuspid annular plane systolic excursion, which was considered the primary outcome. Linear correlations between the right and left ventricular indices, as well as their association with the outcome of death or extracorporeal membrane oxygenation were evaluated. Persistent pulmonary hypertension of newborn was associated with lower tricuspid annular plane systolic excursion (6.81 ± 1.92 vs 9.25 ± 1.30 mm), right-ventricular global longitudinal strain (16.9% ± 5.4% vs -21.6% ± 4.6%); left ventricular ejection fraction (49% ± 7% vs 55% ± 6%), left ventricular global longitudinal strain (-16.7% ± 3.3% vs -21.4% ± 2.0%) (all p < 0.01). Right and left ventricular diastolic and global function was also lower in persistent pulmonary hypertension of newborn, with more pronounced changes seen for the right ventricle. Moderate-to-strong linear correlations were observed between the right and left ventricular functional markers, with right ventricular global longitudinal strain and left ventricular global longitudinal strain being the strongest (r = 0.8). Within persistent pulmonary hypertension of newborn group, hypoxic ischemic encephalopathy was associated with lower right and left ventricular systolic and right ventricular diastolic performance. Tricuspid annular plane systolic excursion (p =0.08) and left ventricular systolic velocity (p = 0.09) tended to be lower in patients who subsequently died/needed extracorporeal membrane oxygenation. CONCLUSIONS: Persistent pulmonary hypertension of newborn is characterized by global cardiac dysfunction, involving both the right and left ventricles, with significant interventricular functional correlation. Cardiac dysfunction early in disease course may identify patients at highest risk of adverse outcome.

Impaired Right Ventricular Performance Is Associated with Adverse Outcome after Hypoxic Ischemic Encephalopathy.

Rationale: Asphyxiated neonates with hypoxic ischemic encephalopathy (HIE) are at risk of myocardial dysfunction; however, echocardiography studies are limited and little is known about the relationship between hemodynamics and brain injury.Objectives: To analyze the association between severity of myocardial dysfunction and adverse outcome as defined by the composite of death and/or abnormal magnetic resonance imaging.Methods: Neonates with HIE undergoing therapeutic hypothermia were enrolled. Participants underwent echocardiography at 24 hours, 72 hours (before rewarming), and 96 hours (after rewarming). Cerebral hemodynamics were monitored by near-infrared spectroscopy and middle cerebral artery Doppler.Measurements and Main Results: Fifty-three patients with a mean gestation and birthweight of 38.8 ± 2.0 weeks and 3.33 ± 0.6 kg, respectively, were recruited. Thirteen patients (25%) had mild encephalopathy, 27 (50%) had moderate encephalopathy, and 13 (25%) had severe encephalopathy. Eighteen patients (34%) had an adverse outcome. Severity of cardiovascular illness (P < 0.001) and severity of neurologic insult (P = 0.02) were higher in neonates with adverse outcome. Right ventricle (RV) systolic performance at 24 hours was substantially lower than published normative data in all groups. At 24 hours, lower tricuspid annular plane systolic excursion (P = 0.004) and RV fractional area change (P < 0.001), but not pulmonary hypertension, were independently associated with adverse outcome on logistic regression. High brain regional oxygen saturation (P = 0.007) and low middle cerebral artery resistive index (P = 0.04) were associated with RV dysfunction on post hoc analysis.Conclusions: RV dysfunction is associated with the risk of adverse outcome in asphyxiated patients with HIE undergoing hypothermia. Echocardiography may be a valuable diagnostic and prognostic tool in this vulnerable population.

Accuracy and reliability of qualitative echocardiography assessment of right ventricular size and function in neonates.

BACKGROUND: Subjective assessment of right ventricular (RV) function by neonatal echocardiography lacks validation. Incorrect diagnostic assignment in patients with suspected pulmonary hypertension (PH) may lead to unnecessary treatment or missed treatment opportunities. METHODS: Six evaluators (experts [n = 3], novice [n = 3]) were asked to independently rate RV characteristics (global function, dilation, and septal flattening) based on standardized echocardiography images. We randomly selected 60 infants, ≥35 weeks gestation at birth, of whom 30 were clinically unwell with acute pulmonary hypertension (aPH) and 30 were healthy controls. aPH was defined by echocardiography presence of right-left shunting across transitional shunts or elevated right ventricular systolic pressure as estimated by the magnitude of the regurgitant jet across the tricuspid valve with impaired oxygenation. Inter-rater comparative evaluation within groups and between groups was performed using Kappa statistics. RESULTS: Global agreement between evaluators for subjective assessment of RV function (0.3 [0.03], P < 0.001), size (0.14 [0.02], P < 0.001), and septal flattening (0.2 [0.02], P < 0.001) was uniformly poor. Agreement in RV function assessment was marginally better for both expert (0.32 [0.08], P < 0.001 vs 0.13 [0.081], and P < 0.001) and novice (0.4 [0.08], P < 0.001 vs 0.06 [0.07], and P < 0.001) evaluators. Overall, the diagnosis of aPH vs control was misclassified in 18% of cases. CONCLUSION: This study demonstrated significant variability in qualitative assessment of RV size and function by trained evaluators, regardless of level of expertise attained. The reliability of objective measures of RV hemodynamics requires prospective evaluation.

Left Ventricular Function in Healthy Term Neonates During the Transitional Period.

OBJECTIVES: To evaluate whether incorporating conventional, tissue Doppler imaging and speckle tracking echocardiography are reliable and can characterize changes in left ventricular (LV) function properly in healthy neonates in the early transitional newborn period. STUDY DESIGN: A prospective observational study was conducted in 50 healthy term neonates with a mean ± SD gestational age and birth weight of 39.3 ± 1.2 weeks and 3.5 ± 0.44 kg, respectively. All infants underwent serial echocardiograms at 15 ± 2 (day 1) and 35 ± 2 hours (day 2) of age. The LV dimensions and various functional indices including tissue Doppler imaging velocities and speckle tracking echocardiography-derived peak longitudinal strain, and systolic and diastolic strain rate were acquired and compared between time points. RESULTS: All measurements were feasible from each scan except speckle tracking echocardiography in 10% and 20% of images on days 1 and 2 of age, respectively. LV dimensions, but not functional measures, demonstrated a small to moderate positive correlation with birth weight. On day 2, a small reduction was observed in LV basal diameter, mitral valve inflow velocity time integral, and systolic velocity of the lateral wall and septum. Other indices remained unchanged. Tissue Doppler imaging-derived functional and flow-derived hemodynamic measures demonstrated the least measurement bias, and strain measurements demonstrated better reliability than strain rate, fractional shortening, and ejection fraction. CONCLUSION: The relative reliability of various echocardiographic indices to quantify LV function in neonates establish a normative dataset and provide evidence for their validity during the first 2 days of life.

The effect of milrinone on right and left ventricular function when used as a rescue therapy for term infants with pulmonary hypertension.

INTRODUCTION: Milrinone may be an appropriate adjuvant therapy for infants with persistent pulmonary hypertension of the newborn. We aimed to describe the effect of milrinone administration on right and left ventricular function in infants with persistent pulmonary hypertension not responding to inhaled nitric oxide after 4 hours of administration. MATERIALS AND METHODS: This is a retrospective review of infants born after or at 34 weeks of gestation with persistent pulmonary hypertension who received milrinone treatment. The primary endpoint was the effect of milrinone on myocardial performance and haemodynamics, including right and left ventricular outputs, tissue Doppler velocities, right ventricle and septal strain, and strain rate. Secondary endpoints examined included duration of inhaled nitric oxide and oxygen support. RESULTS: A total of 17 infants with a mean (standard deviation) gestation and birth weight of 39.8 (2.0) weeks and 3.45 (0.39) kilograms, respectively, were included in the study. The first echocardiogram was performed 15 hours after the commencement of nitric oxide inhalation. Milrinone treatment was started at a median time of 1 hour after the echocardiogram and was associated with an increase in left ventricular output (p=0.04), right ventricular output (p=0.004), right ventricle strain (p=0.01) and strain rate (p=0.002), and left ventricle s` (p<0.001) and a` (p=0.02) waves. There was a reduction in nitric oxide dose and oxygen requirement over the subsequent 72 hours (all p<0.05). CONCLUSION: The use of milrinone as an adjunct to nitric oxide is worth further exploration, with preliminary evidence suggesting an improvement in both oxygenation and myocardial performance in this group of infants.

Assessment and treatment of post patent ductus arteriosus ligation syndrome.

OBJECTIVE: To compare differences in tissue Doppler imaging, global longitudinal strain (GLS), and cardiac troponin T (cTnT) between infants with low (<200 mL/kg/min) and high (>200 mL/kg/min) left ventricular (LV) output 1 hour after duct ligation and assess the impact of milrinone treatment on cardiac output and myocardial performance. STUDY DESIGN: LV function was assessed preoperatively and 1 and 18 hours postoperatively. Infants were categorized into a low-output or a normal-output group based on the echocardiographic assessment of LV output at 1 hour. RESULTS: Thirty infants with a mean gestation of 25.3 weeks were enrolled. LV basal lateral S', basal septal S', and basal right ventricular S' were lower in the low-output group (n = 19) at 1 hour postoperatively, with no significant difference in GLS (low-output -10.3% vs high-output -14.4%, P >.05) or cTnT between the groups. Patients in the low-output group were treated with milrinone, and by 18 hours LV performance recovered to levels comparable with the high output group. cTnT values increased at 18 hours in the whole cohort with no significant difference between the groups. CONCLUSION: Tissue Doppler imaging and GLS provide novel insights and further characterization of myocardial performance immediately after patent ductus arteriosus ligation. A reduction in tissue Doppler-derived LV systolic velocity may further help in monitoring cardiac performance after patent ductus arteriosus ligation and for monitoring the effects of treatment.

Altered Cytokine Endotoxin Responses in Neonatal Encephalopathy Predict MRI Outcomes.

Background: Neonatal encephalopathy (NE) is associated with adverse neurodevelopmental outcome and is linked with systemic inflammation. Pro-inflammatory and anti-inflammatory cytokines are known to play a role in the pathology of NE by activating innate immune cells. Methods: Eighty-seven infants were enrolled including 53 infants with NE of whom 52 received therapeutic hypothermia (TH) and 34 term infant healthy controls (TC). Whole blood sampling was performed in the first 4 days of life, and a 14-spot ELISA Multiplex Cytokine Array was carried out on baseline samples or after stimulation with lipopolysaccharide (LPS) as an additional inflammatory stimulus. The cytokine medians were examined for differences between infants with NE and healthy TC; and then short-term outcomes of Sarnat stage, seizures, and MRI brain were examined within the NE group. The potential of LPS stimulation to predict abnormal MRI was explored using receiver operating characteristic (ROC) curves. Results: At baseline, infants with NE had significantly higher levels of erythropoietin (Epo), interleukin (IL)-6, and IL-1ra and significantly lower vascular endothelial growth factor (VEGF) than had controls. All cytokines were increased after LPS stimulation in infants with NE with an excessive Epo and IL-1ra response than in controls. Infants with NE had lower IL-8, IL-2, IL-6, tumor necrosis factor (TNF)-α, granulocyte-macrophage colony-stimulating factor (GM-CSF), VEGF, and interferon (IFN)-γ than controls had following LPS. GM-CSF and IFN-γ, IL-1ß, IL-1ra, and VEGF were higher on days 1-2 in NE infants with abnormal neuroimaging. GM-CSF, IFN-γ, and TNF-α levels with LPS stimulation were different upon stimulation between normal and abnormal neuroimaging. TNF-α is the only strong cytokine predictor both pre- and post-LPS stimulation of abnormal brain imaging. Conclusions: Altered cytokine responses are found in infants with NE vs. controls, and more significant differences are unmasked by the additional stimulus of LPS, which potentially improves the predictive power of these cytokines for the detection of abnormal MRIs. Infants with NE undergoing TH demonstrate both trained immunity and tolerance, and understanding these responses will facilitate adjunctive immunomodulatory treatments.

Multicentre prospective observational study exploring the predictive value of functional echocardiographic indices for early identification of preterm neonates at risk of developing chronic pulmonary hypertension secondary to chronic neonatal lung disease.

INTRODUCTION: Although chronic pulmonary hypertension (cPH) secondary to chronic neonatal lung disease is associated with increased mortality and respiratory and neurodevelopmental morbidities, late diagnosis (typically ≥36 weeks postmenstrual age, PMA) and the use of qualitative echocardiographic diagnostic criterion (flat interventricular septum in systole) remain significant limitations in clinical care. Our objective in this study is to evaluate the utility of relevant quantitative echocardiographic indices to identify cPH in preterm neonates, early in postnatal course and to develop a diagnostic test based on the best combination of markers. METHODS AND ANALYSIS: In this ongoing international prospective multicentre observational diagnostic accuracy study, we aim to recruit 350 neonates born <27 weeks PMA and/or birth weight <1000 g and perform echocardiograms in the third week of age and at 32 weeks PMA (early diagnostic assessments, EDA) in addition to the standard diagnostic assessment (SDA) for cPH at 36 weeks PMA. Predefined echocardiographic markers under investigation will be measured at each EDA and examined to create a scoring system to identify neonates who subsequently meet the primary outcome of cPH/death at SDA. Diagnostic test characteristics will be defined for each EDA. Pulmonary artery acceleration time and tricuspid annular plane systolic excursion are the primary markers of interest. ETHICS AND DISSEMINATION: Ethics approval has been received by the Mount Sinai Hospital Research Ethics Board (REB) (#16-0111-E), Sunnybrook Health Sciences Centre REB (#228-2016), NHS Health Research Authority (IRAS 266498), University of Iowa Human Subjects Office/Institutional Review Board (201903736), Rotunda Hospital Research and Ethics Committee (REC-2019-008), and UBC Children's and Women's REB (H19-02738), and is under review at Boston Children's Hospital Institutional Review Board. Study results will be disseminated to participating families in lay format, presented to the scientific community at paediatric and critical care conferences and published in relevant peer-reviewed journals. TRAIL REGISTRATION NUMBER: NCT04402645.

Defining "Haemodynamic Significance" of the Patent Ductus Arteriosus: Do We Have All the Answers?

Optimum management of the patent ductus arteriosus (PDA) in preterm infants remains one of the most debated topics within the field of neonatology. Despite numerous observational studies and over 60 randomized control trials, consensus on PDA management remains elusive. In order to make meaningful progress on the controversial issue of PDA management, several key factors must be thoroughly addressed; namely (1) accurate identification of infants at greatest risk of long-term morbidities from PDA exposure, (2) acceptance that the PDA is not a dichotomous entity and an individualised approach to its management is required for each neonate, (3) international consensus on what constitutes a haemodynamically significant PDA and (4) the incorporation of multi-organ assessment when evaluating the impact a PDA may pose on overall neonatal physiology. This review assesses the evidence base available supporting various therapeutic strategies for PDA, the deficits in our current knowledge on the definition of haemodynamic significance and future directions to pursue in order to more successfully address this contentious subject.

Influence of a patent ductus arteriosus on cardiac troponin T levels in preterm infants.

OBJECTIVE: To evaluate the effect of patent ductus arteriosus (PDA) on the myocardium by measuring levels of cardiac troponin T (cTnT), a marker of ischemic myocardial damage. STUDY DESIGN: Eighty infants with a median gestation of 28 weeks (interquartile range ([IQR] = 26.1 to 29.5 weeks) and median birth weight of 1.06 kg (IQR = 0.87 to 1.21 kg) underwent echocardiographic and cTnT assessments at 12 and 48 hours of life. The infants with PDA were treated with ibuprofen or surgical ligation. Follow-up echocardiography and cTnT assay was performed after treatment. RESULTS: The median 12-hour cTnT level was 0.20 microg/L (IQR = 0.11 to 0.40 microg/L). At 48 hours, median cTnT level was significantly higher in the PDA group (n = 45) than in the spontaneous closure group (n = 35) (0.43 vs 0.13 microg/L; P < .001). Following successful treatment, cTnT levels decreased significantly, to 0.10 microg/L (P < .001). cTnT levels correlated significantly with ductal diameter, left atrial-to-aortic diameter ratio, and descending aortic end-diastolic velocity. The receiver operating characteristics curve for detection of PDA through cTnT values had an area under the curve of 0.78 (95% confidence interval = 0.66 to 0.90; P < .001). CONCLUSIONS: cTnT may be a useful marker of ductal significance and treatment response, because it correlates with echocardiographic markers of PDA. Elevated cTnT level may reflect the potential myocardial damage caused by a PDA.

Assessment of myocardial performance in preterm infants less than 29 weeks gestation during the transitional period.

BACKGROUND: The transitional circulation and its effect on myocardial performance are poorly understood in preterm infants. AIMS: We assessed myocardial performance in infants less than 29 weeks gestation in the first 48 h of life using a comprehensive echocardiographic assessment. DESIGN: Infants <29 weeks gestation were prospectively enrolled. Small for gestation, infants on inotropes and/or inhaled nitric oxide and septic infants were excluded. Conventional echocardiography, left ventricular (LV), septal and right ventricular (RV) tissue Doppler imaging (TDI) and tissue Doppler-derived strain and strain rate (SR), tricuspid annular plane systolic excursion (TAPSE) and global RV fractional area change (FAC) were assessed at a median of 10 and 45 h post-delivery. RESULTS: Fifty-four infants with a median [IQR] gestation and birth weight of 26.5 weeks [25.8-28.0 weeks] and 915 g [758-1142 g] were included. There was no change in shortening or ejection fraction across the two time points. Systolic and diastolic TDI of the LV, septum and RV increased across the two time points (all p values ≤ 0.01). There was an increase in septal peak systolic and early diastolic SR (p=0.002). Septal systolic strain and late diastolic SR did not change. With the exception of RV strain and early diastolic SR, all RV functional parameters including SR, late diastolic SR, TAPSE, and FAC increased across the two time points (all p values<0.01). CONCLUSION: Describing the normal hemodynamic adaptations in stable preterm infants during the transitional period provides the necessary information for the assessment of those parameters in various disease states.

Acute changes in myocardial systolic function in preterm infants undergoing patent ductus arteriosus ligation: a tissue Doppler and myocardial deformation study.

BACKGROUND: Ligation of a patent ductus arteriosus (PDA) in preterm infants causes profound hemodynamic changes that can result in low cardiac output syndrome and hypotension. The effect of PDA ligation on left ventricular myocardial function has not been studied using tissue Doppler and myocardial deformation imaging, mainly because of the limited validation of these methods in preterm infants. The primary objective of the present study was to determine the feasibility and reliability (intraobserver and interobserver variability) of tissue Doppler and myocardial deformation imaging for evaluating myocardial function in preterm infants undergoing surgical PDA ligation. Additionally, we sought to study the immediate effect of surgical ligation on the left ventricular tissue Doppler and strain measurements in the first 24 hours after surgery. METHODS: Echocardiography was performed in 19 preterm infants before, 1 hour after, and 18 hours after PDA ligation born at 24-29 weeks of gestation. The tissue Doppler velocities of the lateral tricuspid and lateral and septal mitral valve annuli were obtained. The global and regional longitudinal peak systolic strain values were determined using two-dimensional speckle tracking echocardiography. The results of the three measurement points were compared using repeated measures analysis of variance. The intra- and interobserver variability was assessed using the intraclass correlation coefficient and Bland-Altman analysis. RESULTS: The median gestational age was 25.0 weeks (interquartile range 24.9-25.9) and the birth weight was 750 g (interquartile range 600-810). For the global longitudinal strain, the intraobserver intraclass correlation coefficient was 0.92 (95% CI, 0.78-0.97, P < .001), and the interobserver intraclass correlation coefficient was 0.93 (95% CI, 0.66-0.98, P < .001). Bland-Altman analysis showed no significant bias between the two observers, with good agreement. The systolic and diastolic tissue Doppler velocities of the mitral valve decreased significantly immediately after ligation and remained significantly lower than the preoperative levels at 18 hours. Also, the global longitudinal strain values significantly decreased 1 hour after the procedure (global longitudinal strain before -19.7% ± -3.8% vs -11.5% ± -3.5%; P = .001) but had significantly improved 18 hours after the procedure (-15.1% ± -2.9%, P = .01). CONCLUSIONS: The present study has shown the feasibility and reliability of using tissue Doppler and strain imaging in premature infants with a hemodynamically significant PDA. Significant changes in myocardial function were observed immediately after PDA ligation, suggesting important changes in myocardial performance immediately after ductal ligation.

Neonatologist-performed functional echocardiography in the neonatal intensive care unit.

The use of point-of-care functional ultrasound to assess cardiovascular function is gaining interest in the neonatal intensive care unit (NICU). The modality has been in use in adult intensive care units for some time and has often guided management. Clinical signs such as heart rate, blood pressure, and capillary refill time, which physicians traditionally have relied upon, provide limited insight into the adequacy of systemic blood flow and organ perfusion. Enhanced cardiovascular imaging and hemodynamic evaluation offers novel insights regarding the contribution of the ductus arteriosus, myocardial performance and pulmonary hemodynamics to ongoing clinical instability. In addition, it allows more accurate delineation of the nature of the underlying disease process and facilitates the evaluation of response to therapeutic intervention. This review examines the potential clinical role of ultrasound methods in the NICU; specifically, its applications in different disease states, and how the technology may be introduced safely in the NICU.

Troponin T, N-terminal pro natriuretic peptide and a patent ductus arteriosus scoring system predict death before discharge or neurodevelopmental outcome at 2 years in preterm infants.

BACKGROUND: 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. OBJECTIVE: 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. DESIGN/METHODS: 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. RESULTS: 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). CONCLUSION: 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.