Cardiac Mechanics Evaluation in Preschool-Aged Children with Preterm Birth History: A Speckle Tracking and 4D Echocardiography Study.

Background: The premature-born adult population is set to grow significantly, and prematurity has emerged as an important cardiovascular risk factor. We aimed to comprehensively assess cardiac mechanics and function in a cohort of ex-preterm preschoolers. Methods: Ex-preterm children (<30 weeks of gestation), aged 2 to 5 years, underwent transthoracic 2D, speckle-tracking, and 4D echocardiography. The findings were compared with 19 full-term children. Results: Our cohort of 38 children with prematurity history showed a normal morpho-functional echocardiographic assessment. However, compared to controls, the indexed 3D end-diastolic volumes of ventricular chambers were reduced (left ventricle 58.7 ± 11.2 vs. 67.2 ± 8.5 mL/m2; right ventricle 50.3 ± 10.4 vs. 57.7 ± 11 mL/m2; p = 0.02). Left ventricle global and longitudinal systolic function were worse in terms of fraction shortening (32.9% ± 6.8 vs. 36.5% ± 5.4; p = 0.05), ejection fraction (59.2% ± 4.3 vs. 62.3% ± 3.7; p = 0.003), and global longitudinal strain (-23.6% ± 2.4 vs. -25.5% ± 1.7; p = 0.003). Finally, we found a reduced left atrial strain (47.4% ± 9.7 vs. 54.9% ± 6.8; p = 0.004). Conclusions: Preschool-aged ex-preterm children exhibited smaller ventricles and subclinical impairment of left ventricle systolic and diastolic function compared to term children. Long-term follow-up is warranted to track the evolution of these findings.

Neonatal Enterovirus-Associated Myocarditis in Dizygotic Twins: Myocardial Longitudinal Strain Pattern Analysis.

Enteroviruses (EVs) are the most common causes of viral myocarditis in neonates. Neonatal enterovirus myocarditis manifestations range from nonspecific febrile illness to congestive heart failure and cardiogenic shock with high risk of in-hospital mortality and long-term cardiac sequelae. Early recognition is essential to undertake appropriate therapy and predict outcomes. Echocardiography and echo-derived left ventricular strain measures seem promising for these purposes. We herein report two cases of neonatal enterovirus-associated myocarditis in dichorionic diamniotic twins, with different presentation, clinical course, and intensity of treatments.

Transcatheter closure in preterm infants with patent ductus arteriosus: feasibility, results, hemodynamic monitoring and future prospectives.

Ductal patency of preterm infants is potentially associated with long term morbidities related to either pulmonary overflow or systemic steal. When an interventional closure is needed, it can be achieved with either surgical ligation or a catheter-based approach.Transcatheter PDA closure is among the safest of interventional cardiac procedures and it is the first choice for ductal closure in adults, children, and infants weighing more than 6 kg. In preterm and very low birth weight infants, it is increasingly becoming a valid and safe alternative to ligation, especially for the high success rate and the minor invasiveness and side effects. Nevertheless, being it performed at increasingly lower weights and gestational ages, hemodynamic complications are possible events to be foreseen.Procedural steps, timing, results, possible complications and available monitoring systems, as well as future outlooks are here discussed.

Congenital Diaphragmatic Hernia: Perinatal Prognostic Factors and Short-Term Outcomes in a Single-Center Series.

Background: Many prognostic factors for CDH patients are described and validated in the current literature: the size of diaphragmatic defects, need for patch repair, pulmonary hypertension and left ventricular dysfunction are recognized as the most influencing outcomes. The aim of this study is to analyze the influence of these parameters in the outcome of CDH patients in our department and identify any further prognostic factors. Methods: An observational retrospective single-center study was conducted including all patients treated at our centre with posterolateral CDH between 01.01.1997 and 12.31.2019. The main outcomes evaluated were mortality and length of hospital stay. A univariate and multivariate analysis was performed. Results: We identified 140 patients with posterolateral CDH; 34.8% died before discharge. The overall median length of stay was 24 days. A univariate analysis confirmed that both outcomes are associated with the size of diaphragmatic defects, need for patch repair and presence of spleen-up (p < 0.05). A multivariate analysis identified that the need for patch repair and maximum dopamine dose used for cardiac dysfunction are independent parameters associated with the length of stay only (p < 0.001). Conclusions: In our series, the duration of hospitalization is longer for newborns with CDH treated with higher doses of dopamine for left ventricular dysfunction or needing patch repair in large diaphragmatic defects.

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.

Sonographic Evaluation of the Endotracheal Tube Position in the Neonatal Population: A Comprehensive Review and Meta-Analysis.

Background: Endotracheal intubation in neonates is challenging and requires a high level of precision, due to narrow and short airways, especially in preterm newborns. The current gold standard for endotracheal tube (ETT) verification is chest X-ray (CXR); however, this method presents some limitations, such as ionizing radiation exposure and delayed in obtaining the radiographic images, that point of care ultrasound (POCUS) could overcome. Primary Objective: To evaluate ultrasound efficacy in determining ETT placement adequacy in preterm and term newborns. Secondary Objective: To compare the time required for ultrasound confirmation vs. time needed for other standard of care methods. Search Methods: A search in Medline, PubMed, Google Scholar and in the Cochrane Central Register of Controlled Trials (CENTRAL) was performed. Our most recent search was conducted in September 2021 including the following keywords: "newborn", "infant", "neonate", "endotracheal intubation", "endotracheal tube", "ultrasonography", "ultrasound". Selection Criteria: We considered randomized and non-randomized controlled trials, prospective, retrospective and cross-sectional studies published after 2012, involving neonatal intensive care unit (NICU) patients needing intubation/intubated infants and evaluating POCUS efficacy and/or accuracy in detecting ETT position vs. a defined gold-standard method. Three review authors independently assessed the studies' quality and extracted data. Main Results: We identified 14 eligible studies including a total of 602 ETT evaluations in NICU or in the delivery room. In about 80% of cases the gold standard for ETT position verification was CXR. Ultrasound was able to identify the presence of ETT in 96.8% of the evaluations, with a pooled POCUS sensitivity of 93.44% (95% CI: 90.4-95.75%) in detecting an appropriately positioned ETT as assessed by CXR. Bedside ultrasound confirmation was also found to be significantly faster compared to obtaining a CXR. Conclusion: POCUS appears to be a fast and effective technique to identify correct endotracheal intubation in newborns. This review could add value and importance to the use of this promising technique.

Thrombocytopenia as Type 1 ROP Biomarker: A Longitudinal Study.

This study aimed to prospectively evaluate the association between the appearance and evolution of retinopathy of prematurity (ROP) and selected blood parameters, focusing on platelets count. In total, 157 preterm consecutive babies screened for ROP were included and classified in: ROP necessitating treatment (group ROP1), ROP regressed without therapy (group ROP2) and no ROP (group no-ROP), divided in two phases for each group depending on gestational age. Blood parameters were weekly gathered and referred to postmenstrual age, ROP severity and phase. Platelet count mean values were statistically lower (p < 0.001) during both phases in ROP1 group (179 × 109/L vs. 213 × 109/L in phase 1 and 2, respectively) vs. other groups (ROP2: 286 × 109/L vs. 293 × 109/L; no ROP: 295 × 109/L vs. 313 × 109/L). Platelet count at birth <181 × 109 was statistically associated with Type 1 ROP development and evolution (sensibility = 76.47%, 95% confidence interval 60.0-87.6; specificity = 66.12%, 95% confidence interval 57.3-73.9). In ROP 1 group, a platelets count mean value "spike" (392.6 × 109/L) was documented at 36 weeks of corrected gestational age, preceding the need for treatment performed at a median of 38.1 ± 3.2 weeks. Early birth thrombocytopenia is confirmed as a biomarker of development and progression of ROP requiring treatment. The increase of platelets count at 35-37 weeks of corrected gestational age can be considered a possible clinical biomarker anticipating Type 1 ROP progression in preterm infants.

Ultrasound for Endotracheal Tube Tip Position in Term and Preterm Infants.

BACKGROUND AND OBJECTIVE: Placing an endotracheal tube (ETT) in neonates is challenging and currently requires timely radiographic confirmation of correct tip placement. The objective was to establish the reliability of ultrasound (US) for assessing ETT position in the neonatal intensive care unit (NICU), time needed to do so, and patients' tolerance. METHODS: A prospective study on 71 newborns admitted to our NICU whose ETT placement was evaluated with US (ETT-echo) and confirmed on chest X-rays (CXR). Data were collected by 3 operators (2 neonatologists and a resident in pediatrics). The right pulmonary artery (RPA) was used as a landmark for US. The distance between the tip of the ETT and the upper margin of the RPA was measured using US and compared with the distance between the tube's tip and the carina on the CXR. RESULTS: Seventy-one intubated newborns were included in the study (n = 34 < 1,000 g, n = 18 1,000-2,000 g, n = 19 > 2,000 g). Statistical analysis (Bland-Altman plot and Lin's concordance correlation coefficient) showed an excellent consistency between ETT positions identified on US and chest X-ray. The 2 measures (ETT-echo and CXR) were extremely concordant both in the whole sample and in the subgroups. Minimal changes in patients' vital signs were infrequently observed during US, confirming the tolerability of ETT-echo. The mean time to perform US was 3.2 min (range 1-13). CONCLUSIONS: ETT-echo seems to be a rapid, tolerable, and highly reliable method worth further investigating for future routine use in neonatology with a view to reducing radiation exposure.

Intra-tracheal surfactant/budesonide versus surfactant alone: Comparison of two consecutive cohorts of extremely preterm infants.

OBJECTIVES: To compare the efficacy of intra-tracheal (IT) surfactant/budesonide (SB) with that of surfactant alone (S) in reducing the rate of bronchopulmonary dysplasia (BPD) at 36 weeks post-menstrual age (PMA), we included extremely preterm very low birth weight (VLBW) infants with severe respiratory distress syndrome (RDS) in our tertiary neonatal level of care unit (Padua, Italy). STUDY DESIGN: A retrospective chart review of two cohorts of extremely preterm VLBW neonates (<28+0 gestation weeks, birth weight [BW] < 1500 g) born in two consequent epochs (2017-2018/2018-2019) were compared. The SB group received surfactant (200 mg/kg 1st dose) and budesonide (0.25 mg/kg), while the S group received surfactant alone. RESULTS: Among 68 neonates with RDS Grades III-IV, FiO2 ≥ 0.3 within 12 h of life, 18 were included in each group after matching for perinatal, clinical, and laboratory characteristics. IT SB did not affect the rate of BPD (Vermont Oxford Network, Jensen's, and National Institute of Child Health and Human Development BPD Workshop 2018 definitions), death, BPD, or death at 36 weeks PMA. Hypotension requiring inotropic support within the first 5 days was lower in those receiving the combined treatment (p = .03). The SB group had fewer admissions to pediatric ward due to respiratory causes up to 12 months of corrected age (p = .03). CONCLUSION: The preliminary results of this retrospective study suggest that in extremely preterm VLBW infants, IT SB for severe RDS did not affect the incidence of BPD, death, and BPD or death at 36 weeks PMA, compared to surfactant alone. The combined therapy proved to be safe in this population. Further studies are warranted to explore the role of early IT steroids on respiratory morbidity in preterm infants.

Ibuprofen enantiomers in premature neonates with patent ductus arteriosus: Preliminary data on an unexpected pharmacokinetic profile of S(+)-ibuprofen.

S(+)-ibuprofen (S-IBU) and R(-)-ibuprofen (R-IBU) concentrations were measured in 16 neonates with patent ductus arteriosus during a cycle of therapy (three intravenous doses of 10-5-5 mg kg-1 at 24-h intervals), at the end of the first infusion and 6, 24, 48, and 72 h later. Data were analyzed with a PK model that included enantiomer elimination rate constants and the R- to S-IBU conversion rate constant. The T½ of S-IBU in the newborn was much longer than in adults (41.8 vs. ≈2 h), whereas the T½ of R-IBU appeared to be the same (2.3 h). The mean fraction of R- to S-IBU conversion was much the same as in adults (0.41 vs. ≈0.60). S-IBU concentrations measured 6 h after the first dose were higher than at the end of the infusion in 10 out of 16 cases, and in five cases, they remained higher even after 24 h. This behavior is unprecedented and may be attributable to a rapid R-to-S conversion overlapping with a slow S-IBU elimination rate. In 13 of the 16 neonates, S-IBU concentrations at 48 and/or 72 h were lower than expected, probably due to the rapid postnatal maturation of the newborn's liver metabolism.

Untargeted and Targeted Metabolomic Profiling of Preterm Newborns with EarlyOnset Sepsis: A Case-Control Study.

Sepsis is a major concern in neonatology, but there are no reliable biomarkers for its early diagnosis. The aim of the study was to compare the metabolic profiles of plasma and urine samples collected at birth from preterm neonates with and without earlyonset sepsis (EOS) to identify metabolic perturbations that might orient the search for new early biomarkers. All preterm newborns admitted to the neonatal intensive care unit were eligible for this proof-of-concept, prospective case-control study. Infants were enrolled as "cases" if they developed EOS, and as "controls"if they did not. Plasma samples collected at birth and urine samples collected within 24 h of birth underwent untargeted and targeted metabolomic analysis using mass spectrometry coupled with ultra-performance liquid chromatography. Univariate and multivariate statistical analyses were applied. Of 123 eligible newborns, 15 developed EOS. These 15 newborns matched controls for gestational age and weight. Metabolomic analysis revealed evident clustering of the cases versus controls, with the glutathione and tryptophan metabolic pathways markedly disrupted in the former. In conclusion, neonates with EOS had a metabolic profile at birth that clearly distinguished them from those without sepsis, and metabolites of glutathione and tryptophan pathways are promising as new biomarkers of neonatal sepsis.

Severe retinopathy of prematurity is associated with early post-natal low platelet count.

Pathophysiology of retinopathy of prematurity (ROP) still presents a gap. Lately blood tests parameters of premature infants have been measured at different times of ROP, attempting to detect correlations with ROP development and progression. So far, very early post-natal biomarkers, predictive of ROP outcome, have not been detected. Our purpose is to evaluate, in the earliest post birth blood sample, the correlation between routinely dosed blood parameters and ROP outcome. 563 preterm babies, screened according to ROP guidelines, were included and classified in conformity with ET-ROP study in "Group 1" (ROP needing treatment), "Group 2" (ROP spontaneously regressed) and "noROP" group (never developed ROP). The earliest (within an hour after delivery) blood test parameters routinely dosed in each preterm infant were collected. Platelet count was decreased in Group 1 versus noROP group (p = 0.0416) and in Group 2 versus noROP group (p = 0.1093). The difference of thrombocytopenic infants among groups was statistically significant (p = 0.0071). CRP was higher in noROP versus all ROPs (p = 0.0331). First post-natal blood sample revealed a significant thrombocytopenia in ROP needing treatment, suggesting a role of platelets in the pathophysiology and progression of ROP, possibly considering it as a predictive parameter of ROP evolution.

Perinatal palliative care: a dedicated care pathway.

OBJECTIVE: Ensure access to perinatal palliative care (PnPC) to all eligible fetuses/infants/parents. DESIGN: During 12 meetings in 2016, a multidisciplinary work-group (WG) performed literature review (Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method was applied), including the ethical and legal references, in order to propose shared care pathway. SETTING: Maternal-Infant Department of Padua's University Hospital. PATIENTS: PnPC eligible population has been divided into three main groups: extremely preterm newborns (first group), newborns with prenatal/postnatal diagnosis of life-limiting and/or life-threatening disease and poor prognosis (second group) and newborns for whom a shift to PnPC is appropriate after the initial intensive care (third group). INTERVENTIONS: The multidisciplinary WG has shared care pathway for these three groups and defined roles and responsibilities. MAIN OUTCOME MEASURES: Prenatal and postnatal management, symptom's treatment, end-of-life care. RESULTS: The best care setting and the best practice for PnPC have been defined, as well as the indications for family support, corpse management and postmortem counselling, as well suggestion for conflicts' mediation. CONCLUSIONS: PnPC represents an emerging field within the paediatric palliative care and calls for the development of dedicated shared pathways, in order to ensure accessibility and quality of care to this specific population of newborns.

Survey of PDA management in very low birth weight infants across Italy.

BACKGROUND: The optimal management of PDA in very low birth weight (VLBW) infants is still controversial. Aim of our study was to investigate the management of PDA in the Italian neonatal intensive care units (NICU). METHODS: We conducted an on-line survey study from June to September 2017. A 50-items questionnaire was developed by the Italian Neonatal Cardiology Study Group and was sent to Italian NICUs. RESULTS: The overall response rate was 72%. Diagnosis of PDA was done by neonatologists, cardiologists or both (62, 12 and 28% respectively). PDA significance was assessed by a comprehensive approach in all centers, although we found a heterogeneous combination of parameters and cut-offs used. None used prophylactic treatment. 19% of centers treated PDA in the first 24 h, 60% after the first 24 h, following screening echocardiography or clinical symptoms, 18% after the first 72 h and 2% after the first week. In the first course of treatment ibuprofen, indomethacin and paracetamol were used in 87, 6 and 7% of centers respectively. Median of surgical ligation was 3% (1-6%). CONCLUSIONS: Significant variations exist in the management of PDA in Italy. Conservative strategy and targeted treatment to infants older than 24 h with echocardiographic signs of hemodynamic significance seemed to be the most adopted approach.

Neonatologist performed echocardiography (NPE) in Italian neonatal intensive care units: a national survey.

BACKGROUND: Neonatologist performed echocardiography (NPE) has increasingly been used to assess the hemodynamic status in neonates. Aim of this survey was to investigate the utilization of NPE in Italian neonatal intensive care units (NICUs). METHODS: We conducted an on-line survey from June to September 2017. A questionnaire was developed by the Italian neonatal cardiology study group and was sent to each Italian NICU. RESULTS: The response rate was 77%. In 94% of Italian NICUs functional echocardiography was used by neonatologists, cardiologists or both (57, 15 and 28% respectively). All the respondents used NPE in neonates with patent ductus arteriosus and persistent pulmonary hypertension, 93% in neonates with hypotension or shock, 85% in neonates with perinatal asphyxia, 78% in suspicion of cardiac tamponade, and 73% for line positioning. In 30% of center, there was no NPE protocol. Structural echocardiography in stable and critically ill neonates was performed exclusively by neonatologists in 46 and 36% of center respectively. CONCLUSIONS: NPE is widely used in Italian NICUs by neonatologists. Structural echocardiography is frequently performed by neonatologists. Institutional protocols for NPE are lacking. There is an urgent need of a formal training process and accreditation to standardize the use of NPE.

Update on Postnatal Corticosteroids to Prevent or Treat Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD) is a major complication of premature birth that significantly affects mortality and long-term morbidity in numerous immature infants. Corticosteroids are particularly suitable for treating BPD, as lung inflammation is central to its pathogenesis. Corticosteroids have considerable, fast beneficial effects on lung function in premature infants with lung disease, but they are also associated with several serious adverse effects, which may have a detrimental impact on long-term outcome. Dexamethasone is the most often used corticosteroid for systemic administration. Despite its value in preventing and treating BPD, its use is associated with several alarming short-term effects and, worst of all, with an increased rate of cerebral palsy in the long term. Dexamethasone nonetheless remains an important therapeutic option for infants with severe lung disease beyond the second to third week of life. Hydrocortisone is an important alternative to dexamethasone, as its use does not appear to be associated with any neurotoxic effects. Its efficacy in the prevention and treatment of BPD has yet to be clearly demonstrated, however. Inhaled corticosteroids might reduce lung inflammation with fewer systemic adverse effects; however, a recent, large randomized trial showed that inhaled budesonide was associated with an excess mortality, despite its beneficial respiratory effects. In another study, instilling budesonide together with surfactant in the trachea of intubated infants with severe respiratory distress appeared safe and achieved a significant reduction in the rate of BPD at 36 postmenstrual weeks. This important finding needs to be confirmed in a larger trial currently underway.

Early modifications of cardiac function in preterm neonates using speckle tracking echocardiography.

BACKGROUND AND AIMS: Preterm newborns undergo hemodynamic challenges in the postnatal period. The aim of this study was to investigate myocardial mechanics changes in the postnatal period in preterm infants using speckle tracking echocardiography (STE). MATERIAL AND METHODS: Thirty-nine preterm infants ≤34 weeks' gestation underwent cardiac ultrasound evaluation during the first 96 hours of life. A repeated echocardiogram at 3 weeks of age was performed. Echocardiographic assessment involved left ventricular ejection fraction, mitral E/A ratio, S' and E' velocities, E/E' ratio, tricuspid annular plane systolic excursion (TAPSE), left atrium-to-aorta ratio, ductal diameter and ductal shunt pattern. Left ventricular longitudinal, circumferential and radial strain, apex-basal rotation and twist were measured from the apical 4-chamber and short-axis views using STE. RESULTS: The mean gestational age was 30 ± 2.7 weeks with a mean birth weight of 1318 ± 485 g. Apical segments demonstrated higher longitudinal strain than basal and mid-ones. In all gestational ages, endocardial longitudinal strain was higher than the epicardial. Epicardial longitudinal strain significantly increased during the first 3 weeks, resulting in the change in basal rotation from counterclockwise to clockwise and thus in the acquisition of twist. Deformation parameters were higher in infants with a hemodynamic significant patents ductus arteriosus. CONCLUSIONS: Echocardiographic assessment of myocardial deformation parameters is feasible in preterm infants. Our data suggest that the maturational process of the myocardium is due to the development of the epicardial layer after birth, which allows the acquisition of the twist.

Respiratory Outcome after Preterm Birth: A Long and Difficult Journey.

Despite notable advances in the survival and management of preterm infants in recent decades, chronic lung disease remains a common complication. Approximately one in three infants born preterm (< 32 weeks of gestation) are hospitalized with respiratory problems (mainly due to infections) in their first 2 years of life, and the risk of childhood wheezing is three times higher in this population. By comparison with infants born at term, there seems to be a higher incidence of respiratory morbidity in those born preterm, even in the absence of bronchopulmonary dysplasia (BPD) and in late-preterm babies. Although long-term follow-up data are still not collected systematically, there is evidence of preterm infants' respiratory symptoms, lung function impairments, and radiological abnormalities, tending to persist throughout childhood and into early adulthood. Respiratory conditions associated with preterm birth are often diagnosed and treated as asthma, but the pathophysiological patterns of BPD and asthma are very different. Future research should focus on characterizing preterm infants' pathological pulmonary features by gestational age at birth, and presence or absence of BPD. Improving our current knowledge of the respiratory disorder associated with prematurity might hopefully prompt targeted follow-up protocols, and novel prevention strategies and treatment approaches.