Premature newborns with intraventricular hemorrhage do not have vasospasm pattern by cranial Doppler ultrasound: A pilot study.

Preterm neonates are at risk for neurodevelopmental impairment, especially those with intraventricular hemorrhage (IVH). Cerebral vasospasm (VSP) is a common complication after subarachnoid hemorrhage (SAH) in adult population, but it is unknown if preterm neonates with IVH may develop it. We prospectively enrolled premature newborns < 32 weeks with IVH and without IVH. All patients received serial transcranial sonography through the temporal window of the middle cerebral artery, anterior cerebral artery, posterior cerebral artery, and the internal carotid artery with transcranial Doppler sonography days 2, 4, and 10 of life. Cerebral blood velocities (CBFVs) were measured including median velocity flow (MV), peak systolic velocity (PSV), and maximum end-diastolic velocity (EDV). Resistance index and pulsatility index were calculated. VSP was defined as an increase of 50% in the baseline velocity per day and/or a Lindegaard ratio higher than 3. Fifty subjects were enrolled. None of the patients with IVH showed elevation of MV or a Lindegaard ratio > 3. There were no differences between IVH and without IVH groups regarding resistance index and pulsatility index.    Conclusion: Preterm infants with IVH do not present a pattern of VSP analyzed by Doppler transcranial ultrasound in this pilot study. What is Known: • In adult population with subarachnoid hemorrhage the most treatable cause of cerebral ischemia is due cerebral vasospasm but is unknown if premature newborn may have vasospasm due the extravasation of blood in the context of intraventricular hemorrhage What is New: •In this pilot study we did not find in premature newborn with intraventricular hemorrhage signs of vasoespam measured by transcranial color doppler ultrasound.

Tissue-Tracking Mitral Annular Displacement in Neonates: A Novel Index of Left Ventricular Systolic Function.

OBJECTIVES: To assess the feasibility, accuracy, and reproducibility of tissue-tracking mitral annular displacement (TMAD) compared with other measures of left ventricular systolic function in healthy preterm and term neonates in the transitional period. METHODS: This was a prospective observational study. Two echocardiograms were performed at 24 and 48 hours of life. TMAD, shortening fraction (SF), ejection fraction (EF), s', and global longitudinal strain (GLS) were measured offline. Accuracy to detect impaired GLS was tested by ROC curve analysis. DeLong test was used to compare AUCs. Intra and interobserver reproducibility of the off-line analysis was calculated. RESULTS: Mean ± SD gestational age and weight were 34.2 ± 3.8 weeks and 2162 ± 833 g, respectively. TMAD was feasible in 168/180 scans (93%). At 24 hours the AUC (95% CI) of SF, EF, s', and TMAD (%) was 0.51 (0.36-0.67), 0.68 (0.54-0.82), 0.63 (0.49-0.77), and 0.89 (0.79-0.99) respectively. At 48 hours the AUC (95% CI) of SF, EF, s', and TMAD (%) was 0.64 (0.51-0.77), 0.59 (0.37-0.80), 0.70 (0.54-0.86), and 0.96 (0.91-1.00), respectively. The AUC of TMAD was superior to the AUC of SF, EF, s', at both timepoints (P < .02). Intraclass correlation coefficients (95% CI) of intra and interobserver reproducibility of TMAD were 0.97 (0.95-0.99) and 0.94 (0.88-0.97), respectively. CONCLUSION: TMAD showed improved accuracy and optimal reproducibility in neonates in the first 48 hours of life.

Reply to the comment on "Fluid restriction in management of patent ductus arteriosus in Italy: a nationwide survey".

The Authors Chang Liu B.S and Yuan Shi commented our paper on Fluid restriction in management of patent ductus arteriosus (PDA) in Italy. With our study, we conducted a prospective cross-sectional survey among all Italian Neonatal Intensive Care Units (NICUs) to address conservative management of patent ductus arteriosus (PDA) in preterm infants below 29 weeks' gestational age (GA), with specific regard to fluid restriction (FR). The Authors wondered if the heterogeneity of use of fluid restriction both as a prophylactic tool and as a conservative tool when a hemodynamically significant PDA is diagnosed, was due to economic disparities among areas of the included centers. Conducting a secondary analysis of our data, we observed that if we separately consider the responses of two areas, northern and central-southern Italy, FR is slightly more frequently applied in Central and Southern regions (82%) as compared to Northern regions (78%), although this finding does not reach statistical significance. No correlation between the likelihood to adopt conservative measures and the amount of allowed fluid intake was found. The hypothesis that "less fluid intake resulted in milder clinical and echocardiographic presentations of PDA, and thus a lower rate of pharmacological treatment" cannot be supported by our current study design and might deserve future investigations.

Fluid restriction in management of patent ductus arteriosus in Italy: a nationwide survey.

We aimed at establishing the state of the art in fluid restriction practice in our national setting and providing a foundation for future research efforts. A prospective cross-sectional survey was conducted among all 114 Italian Neonatal Units in order to address conservative management of patent ductus arteriosus (PDA) in preterm infants below 29 weeks' gestational age (GA), with specific regard to fluid restriction. Response rate was 80%. Conservative measures for PDA management are provided in the majority of NICUs and 80% of centers reduce fluid intake in neonates with PDA. No relationship can be found among pharmacologically or surgically treated patients per year and the approach to fluid restriction. The minimum intake administered at regimen when fluid restriction is applied is associated to the ratio between the maximum number of neonates managed pharmacologically and number of admitted < 29 weeks' GA newborns. CONCLUSION: Our survey shows an extreme variability among centers in terms of use of fluid restriction as a prophylactic tool but also in terms of its use (both opportunity and modality) when a hemodynamically significant PDA is diagnosed. This variability, that can be also found in randomized trials and observational studies, suggests that further evidence is needed to better understand its potential beneficial effects and its potential harms such as dehydration, hypotension, decreased end-organ perfusion, and reduced caloric intake. WHAT IS KNOWN: • The lack of demonstrable improvement following the treatment of patent ductus arteriosus has recently paved the way to a more conservative approach. • Fluid restriction is the most commonly applied conservative treatment of PDA. WHAT IS NEW: • Among Italian NICUs an extreme variability in terms of indications, timing and modalities of application of Fluid restriction can be found. • This variability reflects the lack of standardization of this practice and the contrasting evidence on its efficacy.

Comparison among three lung ultrasound scores used to predict the need for surfactant replacement therapy: a retrospective diagnostic accuracy study in a cohort of preterm infants.

Lung ultrasound (LU) has emerged as the imaging technique of choice for the assessment of neonates with respiratory distress syndrome (RDS) at the bedside. Scoring systems were developed to quantify RDS severity and to predict the need for surfactant administration. There is no data on the comparison of the three main LU scores (LUS) proposed by Brat, Raimondi and Rodriguez-Fanjul. Moreover, there is not enough evidence to recommend which score and which cut-off has the best ability to predict surfactant need. The three LUS were compared in terms of ability to predict the need for surfactant and reproducibility in a cohort of very preterm infants. This was an observational, retrospective, multicenter study. Neonates below 32 weeks of gestational age with RDS, on non-invasive ventilation with a LU performed prior to surfactant administration (1-3 h of life) were included. Brat, Raimondi, and Rodriguez-Fanjul's scores were calculated for each patient. Receiver-operating characteristic (ROC) curve analysis was used to assess the ability to predict surfactant administration. K-Cohen test, Bland-Altman, and intraclass correlation coefficients were used to assess the intra and interobserver variability. Fifty-four preterm infants were enrolled. Brat, Raimondi, and Rodriguez-Fanjul scores showed a strong ability to predict the need for surfactant: the AUCs were 0.85 (95% CI 0.74-0.96), 0.85 (95% CI 0.75-0.96), and 0.79 (95% CI 0.67-0.92), respectively. No significant differences have been found between the AUCs using the DeLong test. Brat and Raimondi's scores had an optimal cut-off value > 8, while the Rodriguez-Fanjul's score > 10. The k-Cohen values of intraobserver agreement for Brat, Raimondi, and Rodriguez-Fanjul's scores were 0.896 (0.698-1.000), 1.000 (1.000-1.000), and 0.922 (0.767-1.000), respectively. The k-Cohen values of interobserver agreement were 0.896 (0.698-1.000), 0.911 (0.741-1.000), and 0.833 (0.612-1.000), respectively.Conclusions: The three LUS had an excellent ability to predict the need for surfactant and an optimal intra and interobserver agreement. The differences found between the three scores are minimal with negligible clinical implications. Since the optimal cut-off value differed, the same score should be used consistently within the same center. What is Known: • Lung ultrasound is a useful bedside imaging tool that should be used in the assessment of neonates with RDS • Scoring systems or lung ultrasound scores allow to quantify the severity of the pulmonary disease and to predict the need for surfactant replacement therapy What is New: • The three lung ultrasound scores by Brat, Raimondi and Rodriguez-Fanjul have an excellent ability to predict the need for surfactant replacement therapy, although with different cut-off values • All three lung ultrasound scores had an excellent intra and interobserver reproducibility.

Impact of Aortic Diameter Measurements at Three Anatomical Landmarks on Left Ventricular Output Calculation in Neonates.

OBJECTIVES: To assess reproducibility and accuracy of left ventricular output (LVO) quantifications in neonates, when left ventricular outflow tract diameter (LVOTD) was measured at the hinges of the aortic valve (AV), at the aortic sinus (AS), and at the sinotubular junction (STJ). METHODS: This was an observational study. In the first cohort of very preterm neonates, we assessed intraobserver and interobserver repeatability of LVOTD measured at the AV, AS, and STJ and of the corresponding LVO. In the second cohort of older neonates, we compared paired LVO measurements by echo and magnetic resonance imaging (MRI). RESULTS: In the first cohort of 48 neonates, mean (standard deviation) weight and age at scan were 1046 (302) g and 28.1 (2.7) weeks. Interobserver bias (95% limits of agreement [LOA]) for LVOTD at the AV, AS, and STJ was 0 (-0.3 to 0.3) mm, 0 (-0.7 to 0.7) mm, and 0 (-0.8 to 0.7) mm, respectively. Interobserver bias (95% LOA) for the corresponding LVO was -1.3 (-31 to 33) ml/kg/min, -0.5 (-88 to 87) ml/kg/min, and -7.2 (-83 to 69) ml/kg/min, respectively. In the second cohort of 10 neonates, median (range) weight and age at scan were 1942 (970-3640) g and 37.2 (31.7-39.8) weeks. LVO measured at the AV showed stronger agreement with MRI: bias (LOA) -10.6 (-74 to 52) ml/kg/min, compared to LVO measured at AS and STJ: 194 (-0.5 to 388) ml/kg/min and 43 (-72 to 159) ml/kg/min respectively. CONCLUSIONS: Reproducibility and accuracy of LVO quantification by echo were better when aortic diameter was measured at AV.

Lung ultrasound findings in congenital diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) occurs in approximately 1 in 2500 to 5000 infants. The use of lung ultrasound (LUS) for its diagnosis has been reported in only two case reports. The aim of this study was to report the LUS pattern of CDH in a case series of infants with respiratory distress. This case series was part of a cohort enrolled in a larger prospective observational study. LUS was performed at the point-of-care during the first 24 h of life of the neonates and its operation time was measured. Seven cases (six left and one right CDH) were diagnosed. We found that the pattern of LUS for CDH diagnosis includes (1) partial absence of the hyperechoic line representing the normal diaphragmatic profile, (2) partial absence of the pleural line in the affected hemithorax, (3) absence of A lines in the affected area, (4) presence of multi-layered area with hyperechoic contents in motion (normal gut), and (5) possible presence of parenchymatous organs inside the thorax (i.e., liver or spleen).Conclusion: A description of LUS pattern in infants with CDH is provided. LUS at the point-of-care may allow the prompt diagnosis of CDH and this is particularly useful in cases of missed prenatal diagnosis. What is Known: • Congenital diaphragmatic hernia occurs in approximately 1 in 2500 to 5000 infants but the use of lung ultrasound for its diagnosis has been reported in only two case reports. What is New: • Research provided a description of lung ultrasound pattern in infants with congenital diaphragmatic hernia. • Lung ultrasound at the point-of-care may allow a prompt diagnosis of congenital diaphragmatic hernia, particularly useful in cases of missed prenatal diagnosis.

Effect on cerebral oxygenation of paracetamol for patent ductus arteriosus in preterm infants.

Paracetamol seems to have similar success rates compared with indomethacin and ibuprofen in closing patent ductus arteriosus (PDA) in preterm infants, but with a better safety profile. The aim of our study was to evaluate the possible effects of paracetamol on cerebral oxygenation and cerebral blood flow velocity (CBFV). Infants with gestational age < 32 weeks with hemodynamically significant PDA (hsPDA) were prospectively studied by near infrared spectroscopy (NIRS) after the first dose of paracetamol (15 mg/kg) or ibuprofen (10 mg/kg). Cerebral regional oxygenation (rSO2C) and fractional oxygen extraction ratio (FOEC) were recorded 30 min before (T0) and 60 ± 20 min (T1), 180 ± 30 min (T2), and 360 ± 30 min (T3) after the beginning of drug infusion. Moreover, mean flow velocity (Vmean) and resistance index (RI = PSV-DV/PSV) measured with Doppler ultrasound in pericallosal artery were recorded at the same times. Significant changes in rSO2C and FOEC were not found during the study period within and between the groups. Similarly, Vmean did not vary in infants treated with paracetamol or ibuprofen, while RI decreased in the ibuprofen group. CONCLUSION: The treatment of hsPDA with paracetamol does not affect cerebral oxygenation in very preterm infants; there were no differences in cerebral oxygenation in infants treated with paracetamol or ibuprofen, although in the ibuprofen group, the possible closure progression of PDA was associated to changes of RI. What is Known: • Paracetamol has similar success rates to indomethacin and ibuprofen in closing PDA with a better safety profile since previous studies did not report adverse effects. What is New: • Paracetamol does not affect cerebral oxygenation and perfusion in very preterm infants with PDA and this confirms its good safety profile.

Painful procedures can affect post-natal growth and neurodevelopment in preterm infants.

AIM: This Italian study evaluated whether painful procedures during the first four weeks of life were related to subsequent weight gain, head circumference (HC) and neurodevelopmental outcomes in preterm infants, METHODS: We evaluated the number of invasive procedures that infants born at less than 32 weeks of gestational age (GA) underwent in the Neonatal Intensive Care Unit of Careggi Hospital, Florence, from January to December 2015. Weight and HC were recorded at birth, 36 weeks of PMA and six and 12 months of CA. Neurological outcomes were assessed at six and 12 months of CA using the Bayley Scales of Infant and Toddler Development - Third Edition. RESULTS: We studied 83 preterm infants with a GA of 28 ± 2 weeks and birth weight of 1098 ± 340 g. A higher number of invasive painful procedures were related to a lower HC standard deviation score at 36 weeks of PMA and six and 12 months of CA and with lower cognitive scores at six months. At 12 months, the relationship only remained significant for infants born at less than 28 weeks (p < 0.001). CONCLUSION: Invasive painful procedures affected regular HC growth and short-term cognitive scores in preterm infants in the first year of life.

Peroxisome proliferator-activated receptor-γ agonist pioglitazone reduces the development of necrotizing enterocolitis in a neonatal preterm rat model.

BACKGROUND: Factors affecting innate immunity and acting as inflammatory regulators, such as the nuclear peroxisome proliferator-activated receptors (PPAR) could be crucial in the pathogenesis of necrotizing enterocolitis (NEC). We hypothesized that the PPARγ agonist pioglitazone (PIO) might be effective in preventing the development of NEC and/or reducing its severity. METHODS: We studied preterm rats in which NEC was induced using the hypoxia-hypothermia model. The treatment group (TG; n = 30) received enteral PIO (10 mg/kg/d) for 72 h and the control group (CG; n = 30) did not. Animals were sacrificed 96 h after birth. NEC was diagnosed evaluating histological ileum changes, and mRNA levels of IL-4, IL-12, IL-6, IL-10, INF-γ, and TNF-α cytokines were measured. RESULTS: NEC occurrence was higher in the CG (18/30; 60%) than in the TG (5/30; 16.7%) and was more severe. Proinflammatory IL-12 and INF-γ mRNA levels were significantly lower in the TG than in the CG; conversely, the anti-inflammatory IL-4 mRNA level was significantly higher in the TG than in the CG. CONCLUSION: Our results demonstrate for the first time that PIO is effective in reducing the incidence and severity of NEC and in decreasing renal injuries in a preterm rat model.

Multimodal neurophysiological monitoring in healthy infants born at term: normative continuous somatosensory evoked potentials data.

AIM: To describe accurate, standardized 1h-multimodal neurophysiological monitoring (1h-MNM), while simultaneously recording VEEG, aEEG, and SEP-C bilaterally from median nerves, and to collect neonatal normative SEP-C data related to behavioural states. METHOD: Twenty healthy, term newborn infants (13 males, 7 females; gestational age 37-42wks; mean 39.6wks, standard deviation [SD] 1.3wks) underwent 1h-MNM within 2 days of life, with focus on recording of the SEP-C (band-pass setting 1-100 Hz, rate of stimulation 1.1 Hz, 50 alternate stimuli). RESULTS: 1h-MNM was easily obtained with identification of cervical (N13) and cortical (N1, P1) SEP-C responses in all infants. SEP-C minimal and maximum N1 latencies/N1-P1 amplitudes were identified, bilaterally, during periods of spontaneous sleep active-quiet-active (AS-QS-AS) and quiet-wakefulness. Minimal latencies and amplitudes occurred in 60% of active sleep/quiet-wakefulness, with the maximums in 70% of quiet sleep. The SEP-C mean values were latencies of N13=13.6ms (SD 1.4ms) and N1=33.6ms (SD 3.9ms) to 34.2ms (SD 4.8ms) in left and right hemisphere respectively; central-conduction-time (CCT) (N13-N1), 20.0ms (SD 4.3ms) to 20.6ms (SD 4.8ms); N1-P1 amplitude=4.6ms (SD 2.7ms) to 3.8µV (SD 2.2µV). INTERPRETATION: 1h-MNM can record simultaneously VEEG/aEEG/SEP-C in newborn infants, showing the modulation of SEP cortical responses in relation to behavioural states in all infants studied using an appropriate neonatal method. We emphasize the importance of obtaining neonatal SEP-C normative data to better identify pathological findings in neonatal brain injury.

Perfusion index and left ventricular output correlation in healthy term infants.

Perfusion index (PI) is a non-invasive marker of peripheral perfusion which is detected by an oximeter. We aimed to assess the correlation between PI and left ventricular output (LVO) in healthy term infants at the time of the screening for congenital heart disease (CHD). PI was measured at 48±2 h of life in the infant's right hand (PIrh) and in one foot (PIf) contemporary to SpO2 for CHD screening. Heart ultrasound was performed immediately after the screening procedure for measuring LVO. Forty-nine healthy term infants were studied. PIrh and PIf were 1.9 ± 0.6 and 1.9 ± 0.8, respectively, and their values were significantly correlated (p < 0.0001) with a coefficient r = 0.8. Bland-Altman analysis shows a mean difference of -0.06 ± 0.47 (95%LOA -0.98-0.86). PIrh correlates with LVO (r = 0.68) and LVO/kg (r = 0.61) with an increase of 151 mL/min (95%CI 103-198) of LVO and 42 mL/kg/min (95%CI 26-58) of LVO/kg per point of PIrh. PIf correlates with LVO (r = 0.74) and LVO/kg (r = 0.73) with an increase of 123 mL/min (95%CI 90-155) of LVO and 37 mL/kg/min (95%CI 27-47) of LVO/kg per point of PIf. CONCLUSION: PI is significantly correlated with LVO in healthy term infants. These results support the theoretical potential role of PI in the CHD screening. What is Known: • Perfusion index is an indirect measure of perfusion which depends on cardiac output and peripheral vascular resistance whose normal values have been documented in term and preterm infants in the first days of life. • Perfusion index has been proposed for the screening of congenital heart disease with duct-dependent systemic circulation in term infants. What is New: • Perfusion index shows a significant correlation with the left ventricular output in term infants at the moment of the screening for congenital heart disease. • Perfusion index might have a theoretical role in improving the accuracy of pulse oximetry in the screening of CHD associated to low systemic flow.

Lung Ultrasound for Diagnosing Pneumothorax in the Critically Ill Neonate.

OBJECTIVES: To evaluate the accuracy of lung ultrasound for the diagnosis of pneumothorax in the sudden decompensating patient. STUDY DESIGN: In an international, prospective study, sudden decompensation was defined as a prolonged significant desaturation (oxygen saturation <65% for more than 40 seconds) and bradycardia or sudden increase of oxygen requirement by at least 50% in less than 10 minutes with a final fraction of inspired oxygen ≥0.7 to keep stable saturations. All eligible patients had an ultrasound scan before undergoing a chest radiograph, which was the reference standard. RESULTS: Forty-two infants (birth weight = 1531 ± 812 g; gestational age = 31 ± 3.5 weeks) were enrolled in 6 centers; pneumothorax was detected in 26 (62%). Lung ultrasound accuracy in diagnosing pneumothorax was as follows: sensitivity 100%, specificity 100%, positive predictive value 100%, and negative predictive value 100%. Clinical evaluation of pneumothorax showed sensitivity 84%, specificity 56%, positive predictive value 76%, and negative predictive value 69%. After sudden decompensation, a lung ultrasound scan was performed in an average time of 5.3 ± 5.6 minutes vs 19 ± 11.7 minutes required for a chest radiography. Emergency drainage was performed after an ultrasound scan but before radiography in 9 cases. CONCLUSIONS: Lung ultrasound shows high accuracy in detecting pneumothorax in the critical infant, outperforming clinical evaluation and reducing time to imaging diagnosis and drainage.

Early fresh-frozen plasma transfusion decreases the risk of retinopathy of prematurity.

BACKGROUND: Insulin-like growth factor 1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) play a main role in the pathogenesis of retinopathy of prematurity (ROP). Fresh-frozen plasma (FFP) from adult donors may be an actual source of IGF-1 and IGFBP-3 because it contains higher concentrations. The objective was to evaluate whether FFP transfusions can decrease the occurrence of ROP in a cohort of preterm infants. STUDY DESIGN AND METHODS: We retrospectively analyzed data from 218 infants with gestational age of less than 29 weeks who either received FFP or did not and correlated this procedure to the development of any grade of ROP. RESULTS: Logistic regression analysis demonstrated that two or more transfusions of FFP was effective in decreasing the risk of development of any grade of ROP (relative risk, 0.46; 95% confidence interval, 0.23-0.93). Other factors that affected the risk of ROP were gestational age, birthweight, antenatal steroid treatment, FiO2 of at least 0.40, mechanical ventilation, and sepsis. CONCLUSIONS: We found that two or more transfusions of FFP in the first week of life decrease the risk of developing any grade of ROP in preterm infants with gestational age of less than 29 weeks.

Left atrial strain assessment unveils left ventricular diastolic dysfunction in neonates with transient tachypnea of the newborn: A prospective observational study.

INTRODUCTION: An inadequate clearance of lung fluid plays a key role in the pathogenesis of transient tachypnea of the newborn (TTN). OBJECTIVES: To evaluate if left ventricular diastolic dysfunction contributes to reduced clearance of lung fluid in TTN. MATERIALS AND METHODS: This was a prospective, observational study. Echocardiography and lung ultrasound were performed at 2, 24 and 48 h of life (HoL) to assess biventricular function and calculate lung ultrasound score (LUS). Left atrial strain reservoir (LASr) provided surrogate measurement of left ventricular diastolic function. RESULTS: Twenty-seven neonates with TTN were compared with 27 controls with no difference in gestation (36.1 ± 2 vs. 36.9 ± 2 weeks) or birthweight (2508 ± 667 vs. 2718 ± 590 g). Biventricular systolic function was normal in both groups. LASr was significantly lower in cases at 2 (21.0 ± 2.7 vs. 38.1 ± 4.4; p < 0.01), 24 (25.2 ± 4.5 vs. 40.6 ± 4.0; p < 0.01) and 48 HoL (36.5 ± 5.8 and 41.6 ± 5.2; p < 0.01), resulting in a significant group by time interaction (p < 0.001), after adjusting for LUS and gestational diabetes. A logistic regression model including LUS, birth weight and gestational diabetes as covariates, showed that LASr at 2 HoL was a predictor of respiratory support at 24 HoL, with an adjusted odds ratio of 0.60 (CI 0.36-0.99). CONCLUSIONS: LASr was reduced in neonates with TTN, suggesting diastolic dysfunction, that may contribute to the delay in lung fluid clearance.

Global longitudinal strain is an informative index of left ventricular performance in neonates receiving intensive care.

Echocardiographic assessment of left ventricular function is crucial in NICU. The study aimed to compare the accuracy and agreement of global longitudinal strain (GLS) with conventional measurements. Real-life echocardiograms of neonates receiving intensive care were retrospectively reviewed. Shortening fraction (SF), ejection fraction (EF) and S' measurements were retrieved from health records. GLS was calculated offline from stored images. The association with stroke volume indexed for body weight (iSV) was evaluated by regression analysis. The diagnostic ability to identify uncompensated shock was assessed by ROC curve analysis. Cohen's κ was run to assess agreement. 334 echocardiograms of 155 neonates were evaluated. Mean ± SD gestational age and birth weight were 34.5 ± 4.1 weeks and 2264 ± 914 g, respectively. SF, EF, S' and GLS were associated with iSV with R2 of 0.133, 0.332, 0.252 and 0.633, (all p < .001). Including all variables in a regression model, iSV prediction showed an adjusted R2 of 0.667, (p < .001). GLS explained 73% of the model variance. GLS showed a better ability to diagnose uncompensated shock (AUC 0.956) compared to EF, S' and SF (AUC 0.757, 0.737 and 0.606, respectively). GLS showed a moderate agreement with EF (κ = .500, p < .001) and a limited agreement with S' and SF (κ = .260, p < .001, κ = .242, p < .001). GLS was a more informative index of left ventricular performance, providing the rationale for a more extensive use of GLS at the cotside.

External Validation of a Multivariate Model for Targeted Surfactant Replacement.

INTRODUCTION: Early targeted surfactant therapy for preterm infants is recommended but the best criteria to personalize treatment are unclear. We validate a previously published multivariate prognostic model based on gestational age (GA), lung ultrasound score (LUS), and oxygen saturation to inspire oxygen fraction ratio (SatO2/FiO2) using an independent data set. METHODS: Pragmatic, observational study in 10 Italian and Spanish NICUs, including preterm babies (250 and 336 weeks divided into 3 GA intervals) with clinical signs of respiratory distress syndrome and stabilized on CPAP. LUS and SatO2/FiO2 were collected soon after stabilization. Their prognostic accuracy was evaluated on the subsequent surfactant administration by a rigorously masked physician. RESULTS: One hundred seventy-five infants were included in the study. Surfactant was given to 74% infants born at 25-27 weeks, 38.5% at 28-30 weeks, and 26.5% at 31-33 weeks. The calibration curve comparing the validation and the development populations showed significant overlap with an intercept = 0.08, 95% CI (-0.34; 0.5) and a slope = 1.53, 95% CI (1.07-1.98). The validation cohort had a high predictive accuracy. Its ROC curve showed an AUC = 0.95, 95% CI (0.91-0.99) with sensitivity = 0.93, 95% CI (0.83-0.98), specificity = 0.81, 95% CI (0.73-0.88), PPV = 0.76, 95% CI (0.65-0.84), NPV = 0.95, 95% CI (0.88-0.98). LUS ≥9 demonstrated the highest sensitivity (0.91, 95% CI [0.82-0.97]) and specificity = 0.81, 95% CI (0.72-0.88) as individual predictor. LUS and SatO2/FiO2 prognostic performances varied with GA. CONCLUSION: We validated a prognostic model based on LUS and Sat/FiO2 to facilitate early, customized surfactant administration that may improve respiratory management of preterm neonates.

To B or not to B. The rationale for quantifying B-lines in pediatric lung diseases.

Lung ultrasound (LUS) is emerging as adjunct tool to be used during clinical assessment. Among the different hallmarks of LUS, B-lines are well known artifacts, which are not correlated with identifiable structures, but which can be used for pathological classification. The presence of multiple B-lines is a sonographic sign of lung interstitial syndrome. It has been demonstrated in adults that there is a direct correlation between the number of B-lines and the severity of the interstitial involvement of lung disease. Counting B-lines is an attempt to enrich the clinical assessment and clinical information, beyond obtaining a simple dichotomous answer. Semiquantitative or quantitative B-line assessment has been shown to correlate with fluid overload and demonstrated prognostic implications in specific neonatal and pediatric conditions. LUS with quantitative B-lines assessment is promising. Current evidence allows for quantification of B-lines in a limited number of neonatal and pediatric diseases.