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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.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.• 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.• 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.

Lung ultrasound (LU) is a noninvasive, bedside imaging technique that is attracting growing interest in the evaluation of neonatal respiratory diseases. We conducted a nationwide survey of LU usage in Italian neonatal intensive care units (NICUs).A structured questionnaire was developed and sent online to 114 Italian NICUs from June to September 2021.The response rate was 79%. In the past 4 years (range: 2-6), LU has been adopted in 82% of Italian NICUs. It is the first-choice diagnostic test in 23% of the centers surveyed. The main LU diagnostic applications reported were: pneumothorax (95%), respiratory distress syndrome (89%), transient tachypnea of the newborn (89%), plural effusion (88%), atelectasis (66%), pneumonia (64%), bronchopulmonary dysplasia (43%), congenital pulmonary airway malformation (41%), and congenital diaphragmatic hernia (34%). Thirty percent of participating centers calculated LU score routinely, but only seven units used it to predict the need for surfactant replacement. Sixty-six percent of respondents learned the LU technique via a self-training process, while 34% of them visited an expert in the field for one-to-one tuition.LU has a widespread use in Italian NICUs. However, the use of LU is extremely heterogeneous among centers. There is an urgent need to ensure standardization of clinical practice guidelines and to design and implement a formalized and accredited training program.

Background Previous research shows that a lung ultrasound score (LUS) can anticipate CPAP failure in neonatal respiratory distress syndrome. Research Question Can LUS also predict the need for surfactant replacement? Study Design and Methods Multicenter, pragmatic study of preterm neonates who underwent lung ultrasound at birth and those given surfactant by masked physicians, who also were scanned within 24 h from administration. Clinical data and respiratory support variables were recorded. Accuracy of LUS, oxygen saturation to F io 2 ratio, F io 2, and Silverman score for surfactant administration were evaluated using receiver operating characteristic curves. The simultaneous prognostic values of LUS and oxygen saturation to F io 2 ratio for surfactant administration, adjusting for gestational age (GA), were analyzed through a logistic regression model. Results Two hundred forty infants were enrolled. One hundred eight received at least one dose of surfactant. LUS predicted the first surfactant administration with an area under the receiver operating characteristic curve (AUC) of 0.86 (95% CI, 0.81-0.91), cut off of 9, sensitivity of 0.79 (95% CI, 0.70-0.86), specificity of 0.83 (95% CI, 0.76-0.89), positive predictive value of 0.79 (95% CI, 0.71-0.87), negative predictive value of 0.82 (95% CI, 0.75-0.89), positive likelihood ratio of 4.65 (95% CI, 3.14-6.89), and negative likelihood ratio of 0.26 (95% CI, 0.18-0.37). No significant difference was shown among different GA groups: 25 to 27 weeks’ GA (AUC, 0.91; 95% CI, 0.84-0.99), 28 to 30 weeks’ GA (AUC, 0.81; 95% CI, 0.72-0.91), and 31 to 33 weeks’ GA (AUC, 0.88; 95% CI, 0.79-0.95), respectively. LUS declined significantly within 24 h in infants receiving one surfactant dose. When comparing F io 2, oxygen saturation to F io 2 ratio, LUS, and Silverman scores as criteria for surfactant administration, only the latter showed a significantly poorer performance. The combination of oxygen saturation to F io 2 ratio and LUS showed the highest predictive power, with an AUC of 0.93 (95% CI, 0.89-0.97), regardless of the GA interval. Interpretation LUS is a reliable criterion to administer the first surfactant dose regardless of GA. Its association with oxygen saturation to F io 2 ratio significantly improves the prediction power for surfactant need.

Extremely preterm birth is associated with a high risk of chronic pulmonary insufficiency of prematurity (CPIP). Lung ultrasound score (LUS) proved capable to characterise CPIP progression beyond the acute setting, but still, post-discharge data remain lacking. We hypothesised a priori that LUS in both BPD and no-BPD infants declines with postnatal age from birth through early infancy. This observational retrospective cohort study included preterm infants 32 gestational weeks, who underwent the follow-up for CPIP. LUS was assessed from birth to 8 months postnatal age, over antero-lateral (LUS) and posterior (pLUS) pulmonary areas, placing the transducer longitudinally over the midclavicular and midaxillary lines and medial to the scapular line respectively. Extended LUS (eLUS) including LUS and pLUS was calculated. The primary outcome was LUS time course. Secondary outcomes included the correlation between LUS and pLUS. Sixty-two infants were included: 22 (35.5%) in the BPD group and 40 (64.5%) in the no-BPD group. BPD group infants were smaller (weight 841 g (± 228) vs 1226 (± 328), p 0.001) and younger (26.8 weeks (± 2.0) vs 28.9 (± 1.9), p 0.001). LUS declined over time in the entire population (ß = - 1.75, p 0.001) and in both no-BPD and BPD groups (ß = - 1.64, p 0.001 and ß = - 1.93, p 0.001, respectively). eLUS declined correspondingly (p 0.001). LUS and likewise eLUS were significantly different between BPD and no-BPD groups over time (p 0.001). Conclusion: LUS trajectory progressively decreased from birth to early infancy. BPD cohort tracked higher, implying a worse respiratory status. pLUS had a similar timepoint course, adding no further information to LUS. To the best of our knowledge, this is the first study that describes preterm LUS time course after discharge. LUS may help track the CPIP progression. What is Known: • Extremely preterm birth is associated with high risk of chronic pulmonary insufficiency of prematurity (CPIP). • Several studies investigated the ability of lung ultrasound score (LUS) to characterize CPIP progression beyond the acute setting, still post-discharge data remain lacking. What is New: • LUS trajectory progressively decreases from birth to early infancy; BPD cohort tracks higher, implying a worse respiratory status. pLUS has similar timepoint course, adding no further information to LUS. • The use of LUS may contribute to better characterising and monitoring CPIP in BPD and no-BPD infants.

Neonatologist-performed echocardiography (NPE) is an established tool for bedside hemodynamic evaluation, including pulmonary hypertension (PH). PH may complicate bronchopulmonary dysplasia (BPD) course. Aims of this retrospective study were to assess the feasibility of NPE follow-up of infants with BPD and to describe the course of PH of infants with moderate/severe BPD. Preterm infants32 gestational weeks or birthweight ≤1500 g with moderate/severe BPD underwent NPE follow-up, from 36 weeks postmenstrual age up to 8 months postnatal age. Twenty-three preemies were included (birth weight 840 (213) g, gestational age 26.8 (2.3) weeks); 12/23 developed mild PH, 2/12 after discharge. PH resolved at 8.9 (3.9) months. Clinical and echocardiographic variables did not differ between infants with and without PH, except pulmonary artery acceleration time (PAAT) and PAAT/right ventricle ejection time (RVET) ratio (PAAT: 36 weeks, 68.9 (11.9) vs 52.0 (19.1), p = 0.0443; 6 months: 83.9 (38.9) vs 74.8 (16.9), p = 0.0372). No deaths or admissions for PH were reported. Neonatologist's Image Quality Assessment score attributed by the cardiologist assumed as gold standard was adequate or optimal (9.5/14 total score); inter-rater agreement was excellent (ICC 0.974).Conclusions: NPE follow-up seems to be feasible and safe in both intensive care and outpatient clinic. Mild PH is frequently detected in moderate/severe BPD, with good prognosis. What is Known: • Preterm infants with bronchopulmonary dysplasia (BPD) may develop pulmonary hypertension (PH) and have a late diagnosis. • Neonatologist-performed echocardiography (NPE) is an established tool for bedside hemodynamic evaluation of the neonate. What is New: • To our knowledge this is the first study of NPE follow-up of moderate/severe BPD, describing the course of mild PH from diagnosis to its resolution. • NPE follow-up of BPD seems to be safe and practicable, in both intensive care and outpatient clinic, as long as neonatologists maintain a sound collaboration with pediatric cardiologists.

B-lines in lung ultrasound (LU) are non-specific but highly informative sign of interstitial pulmonary oedema (iPE). Sustained exposure to a high-volume left-to-right patent ductus arteriosus (PDA) shunt is associated with iPE. Cardiorespiratory deterioration, named post-ligation cardiac syndrome (PLCS), may follow surgical ligation between 6 and 12 h post-operatively. We conducted a pilot longitudinal evaluation of peri-procedural LU score change. Infants 32-week gestational age or 1500-g birthweight undergoing PDA ligation, where pre-, 1 h and 6-12 h LU were performed, were included. Two independent raters evaluated LU score (LUS). Neonatologist performed echocardiography (NPE) was performed concurrently to appraise changes in left ventricular output (LVO). Milrinone was initiated if LVO was 200 mL/kg/min 1 h after surgery, to prevent PLCS. The primary outcome was peri-procedural LUS change. Secondary outcomes included PLCS. Five infants were included (birthweight 787(88) g; gestational age 25.6(0.7) weeks). Postnatal age and weight at the intervention were 41(14) days and 1175(295) g. All infants, but one, received milrinone prophylaxis. None of the patients developed PLCS or required rescue HFOV. Post-interventional LUS were lower compared to pre-operative LUS (p = 0.041 vs 1 h, p = 0.042 vs 6-12 h). A concurrent fall post-operative LVO was noted (p 0.05 vs pre-operative).A sustained fall in LUS after PDA ligation was identified, which most likely reflects reduction in pulmonary blood flow and interstitial edema. Changes in LUS paralleled changes in LVO, suggesting physiologic linkage. These data suggest that LU may be a useful tool to guide monitoring the biologic nature of pulmonary disease after PDA ligation.• Sustained exposure to a high-volume left-to-right patent ductus arteriosus (PDA) shunt is associated with interstitial pulmonary oedema. • In the most immature patients, cardiorespiratory deterioration, named post-ligation cardiac syndrome, presents 6-12 h post-operatively.• An early and sustained fall in lung ultrasound score (LUS) after PDA ligation most likely reflects reduction in pulmonary blood flow and interstitial oedema. LUS changes parallel changes in left ventricular output, suggesting linkage. • LU is a promising adjunctive tool in the post-operative management of PDA ligation.

BACKGROUND AND OBJECTIVES: The utility of a lung ultrasound score (LUS) has been described in the early phases of neonatal respiratory distress syndrome (RDS). We investigated lung ultrasound as a tool to monitor respiratory status in preterm neonates throughout the course of RDS. METHODS: Preterm neonates, stratified in 3 gestational age cohorts (25–27, 28–30, and 31–33 weeks), underwent lung ultrasound at weekly intervals from birth. Clinical data, respiratory support variables, and major complications (sepsis, patent ductus arteriosus, pneumothorax, and persistent pulmonary hypertension of the neonate) were also recorded. RESULTS: We enrolled 240 infants in total. The 3 gestational age intervals had significantly different LUS patterns. There was a significant correlation between LUS and the ratio of oxygen saturation to inspired oxygen throughout the admission, increasing with gestational age (b = −0.002 [P < .001] at 25–27 weeks; b = −0.006 [P < .001] at 28–30 weeks; b = −0.012 [P < .001] at 31–33 weeks). Infants with complications had a higher LUS already at birth (12 interquartile range 13–8 vs 8 interquartile range 12–4 control group; P = .001). In infants 25 to 30 weeks’ gestation, the LUS at 7 days of life predicted bronchopulmonary dysplasia with an area under the curve of 0.82 (95% confidence interval 0.71 to 93). CONCLUSIONS: In preterm neonates affected by RDS, the LUS trajectory is gestational age dependent, significantly correlates with the oxygenation status, and predicts bronchopulmonary dysplasia. In this population, LUS is a useful, bedside, noninvasive tool to monitor the respiratory status.

Previous research shows that a lung ultrasound score (LUS) can anticipate CPAP failure in neonatal respiratory distress syndrome.Can LUS also predict the need for surfactant replacement?Multicenter, pragmatic study of preterm neonates who underwent lung ultrasound at birth and those given surfactant by masked physicians, who also were scanned within 24 h from administration. Clinical data and respiratory support variables were recorded. Accuracy of LUS, oxygen saturation to FioTwo hundred forty infants were enrolled. One hundred eight received at least one dose of surfactant. LUS predicted the first surfactant administration with an area under the receiver operating characteristic curve (AUC) of 0.86 (95% CI, 0.81-0.91), cut off of 9, sensitivity of 0.79 (95% CI, 0.70-0.86), specificity of 0.83 (95% CI, 0.76-0.89), positive predictive value of 0.79 (95% CI, 0.71-0.87), negative predictive value of 0.82 (95% CI, 0.75-0.89), positive likelihood ratio of 4.65 (95% CI, 3.14-6.89), and negative likelihood ratio of 0.26 (95% CI, 0.18-0.37). No significant difference was shown among different GA groups: 25 to 27 weeks' GA (AUC, 0.91; 95% CI, 0.84-0.99), 28 to 30 weeks' GA (AUC, 0.81; 95% CI, 0.72-0.91), and 31 to 33 weeks' GA (AUC, 0.88; 95% CI, 0.79-0.95), respectively. LUS declined significantly within 24 h in infants receiving one surfactant dose. When comparing FioLUS is a reliable criterion to administer the first surfactant dose regardless of GA. Its association with oxygen saturation to Fio

In many preterm infants, the ductus arteriosus remains patent beyond the first few days of life. This prolonged patency is associated with numerous adverse outcomes, but the extent to which these adverse outcomes are attributable to the hemodynamic consequences of ductal patency, if at all, has not been established. Different treatment strategies have failed to improve short-term outcomes, with a paucity of data on the correct diagnostic and pathophysiological assessment of the patent ductus arteriosus (PDA) in association with long-term outcomes. Echocardiography is the selected method of choice for detecting a PDA, assessing the impact on the preterm circulation and monitoring treatment response. PDA in a preterm infant can result in pulmonary overcirculation and systemic hypoperfusion, Therefore, echocardiographic assessment should include evaluation of PDA characteristics, indices of pulmonary overcirculation with left heart loading conditions, and indices of systemic hypoperfusion. In this review, we provide an evidence-based overview of the current and emerging ultrasound measurements available to identify and monitor a PDA in the preterm infant. We offer indications and limitations for using Neonatologist Performed Echocardiography to optimize the management of a neonate with a PDA.

Background: We hypothesize that urine levels might be reliable to assess the therapeutic range of caffeine. Objectives: We correlated plasma and urinary levels of caffeine in preterm infants treated with this drug for apnea of prematurity. Methods: Infants (n=56) were given a loading dose of caffeine citrate (10 mg/kg, per os) and 24 h later a maintenance dose (2 mg/kg, per os, once a day). Plasma and urinary levels of caffeine were determined 24 h after the loading dose (before administration of the maintenance dose) and then weekly. Results: Plasma and urinary levels correlate at all examined ages: '29 weeks (r=0.92, P