Lung ultrasound predicts surfactant need in neonates on different respiratory support: an international diagnostic accuracy study Francesco Raimondi, Almudena Alonso Ojembarrena, Irene Gutierrez Rosa, Fabio Meneghin, Rebeca Gregorio Hernandez, Javier Rodriguez Fanjul, Chiara Colinet, Fiorella Migliaro, Marco Fossati, Luca Bonadies, Stefano Nobile, Giovanni Vento, Eugenio Baraldi, Stefano Martinelli, Gianluca Lista, Manuel Sanchez Luna, Mario Meliande, Pasquale Dolce, Peter G. Davis, Letizia Capasso Respiratory Research, 2026 An early lung ultrasound score (eaLUS) predicts surfactant administration in neonates of any gestational age with respiratory distress syndrome stabilized on CPAP. Whether this is also true for more unwell infants, non invasively and invasively ventilated, is not known. To assess whether an eaLUS may predict surfactant replacement in infants on different respiratory support modes (CPAP, nasal ventilation and mechanical ventilation). We also investigated eaLUS as a potential marker of unfavorable respiratory outcomes. Prospective, international, multicenter diagnostic study conducted from March 2024 to March 2025 in seven, level III Italian and Spanish neonatal intensive care units. Participants: neonates of any gestational age presenting with respiratory distress, enrolled within 2 h of birth and before the administration of surfactant. Intervention: eaLUS calculated within the first 2 h of life masked to attending physician evaluating both the type of respiratory support and the need for surfactant administration. Main outcome: prognostic accuracy of eaLUS to predict surfactant administration overall and in three subgroups based on early respiratory stabilization strategy (CPAP, NIV and MV). As secondary outcomes we investigated the accuracy of oxygen inspiratory fraction (FiO2) > 0.3 by mode of respiratory support to predict surfactant need. Additionally, logistic regression analysis was used to investigate the link between eaLUS with prolonged mechanical ventilation and death or BPD as secondary outcomes. We enrolled 229 infants stabilized on CPAP (n = 117), nasal ventilation (n = 58) and mechanical ventilation (n = 54). eaLUS had good prognostic accuracy in the total population (AUC, 0.86; 95% CI, 0.81–0.91). Despite the wide gap of mean airway pressure (MAP) across the population, eaLUS and MAP were only moderately correlated (rho = 0.39; p < 0.001). Optimal thresholds for surfactant replacement were slightly different (LUS ≥ 8 for CPAP; LUS ≥ 9 for nasal ventilation; LUS ≥ 10 for mechanical ventilation). FiO2 > 0.3 was a less accurate predictor of surfactant replacement. eaLUS was significantly associated to prolonged mechanical ventilation beyond both 72 and 168 h. Finally, eaLUS emerged as an independent predictor of BPD or death. An early LUS accurately predicts surfactant replacement in neonates non invasively and invasively ventilated and it is a noninvasive imaging prognostic marker of disease severity and adverse respiratory outcomes in this population. ISRCTN Registry (number ISRCTN10205806).
Bronchopulmonary dysplasia and extremely preterm birth: time for a broader perspective on long-term outcomes Luca Bonadies, Lorenzo Zanetto, Valentina Agnese Ferraro, Laura Moschino, Alberto Papi, Eugenio Baraldi European Respiratory Review, 2026 Bronchopulmonary dysplasia is a hallmark respiratory complication of prematurity and remains a major health determinant of individuals born very preterm. Its impact, however, extends far beyond the neonatal period and far beyond the lungs. Children, adolescents and adults born very preterm often follow diverse developmental trajectories that diverge from typical postnatal growth. These trajectories often display early airflow limitation, as well as features of increased cardiovascular vulnerability and altered multisystemic profiles. Although common respiratory labels such as asthma are often applied to these patients, evidence highlights distinct pathobiological mechanisms rooted in arrested alveolar and vascular growth, with a possible contribution from persistent airway inflammation and oxidative stress. Extrapulmonary involvement, including cardiovascular, neurodevelopmental, neurosensory, renal and metabolic domains, further shapes long-term outcomes and should be systematically integrated into long-term monitoring. Yet, despite improving survival and growing recognition of this multisystemic burden, current evidence remains insufficient to design a dedicated, holistic, multidisciplinary follow-up programme tailored to the diverse subgroups of preterm-born individuals. Increasing awareness among healthcare professionals of the long-term implications of prematurity is essential to ensure that these patients receive appropriate and coordinated attention. Emerging lines of research, spanning new preventive and therapeutic options, advanced imaging, mechanistic studies, and long-term cohort designs, hold promise in elucidating the biological determinants of disease. Integrating these insights into clinical pathways, together with sustained implementation of family-centred care models, will be crucial to optimise organ function trajectories, delay deterioration and ultimately improve the quality of life of the growing population of survivors of prematurity.
Definitions of Bronchopulmonary Dysplasia Do Not Influence Quantitative Lung Ultrasound Predictive Accuracy Daniele De Luca, Luca Bonadies, Guillermo Ramos-Noguera, Teresa Silva-García, Costanza Renata Neri, Francesco Chiarelli, Eugenio Baraldi, Almudena Alonso-Ojembarrena Neonatology, 2026 Introduction: Quantitative lung ultrasound (LUS) predicts bronchopulmonary dysplasia (BPD), but variability in BPD definitions raises concerns about its predictive consistency. We hypothesized that predictive accuracy of LUS would remain stable regardless of the definition applied. Methods: In this prospective, multicenter cohort study, preterm infants ≤30 weeks of gestation underwent extended LUS (eLUS, adj-eLUS) aeration score at days 10, 21, and 28. BPD was assessed at 36 weeks of postmenstrual age using Jobe and Bancalari (2001), NICHD (2018), and Jensen (2019) definitions. Receiver operating characteristic (ROC) analysis compared predictive performance (areas under ROC curve [AUC]) across definitions. Results: Among 337 infants (mean gestational age: 27 weeks, mean birth weight: 941 g), BPD incidence ranged from 22.8 to 25.8% depending on definition. AUCs for BPD prediction ranged between 0.732 and 0.832. The mean difference (ΔAUC) between definitions was minimal (≈0.02, 95% confidence interval: 0.01–0.03) and nonsignificant at all time points. Conclusions: Quantitative LUS reliably predicts BPD regardless of its definition, and this support its use in early respiratory care and monitoring.
Lung aeration and gas exchange in preterm infants developing moderate-to-severe bronchopulmonary dysplasia: a multicentre prospective study from the PATH-BPD cohort Daniele De Luca, Luca Bonadies, Costanza Neri, Barbara Loi, Teresa Maria Silva-Garcia, Guillermo Ramos Noguera, Laura Vivalda, Giulia Res, Maria de las Nieves Cidoncha-Fuertes, Carlos Baena-Palomino, Lorenzo Zanetto, Luca Vedovelli, Dario Gregori, Eugenio Baraldi, Almudena Alonso-Ojembarrena Lancet Regional Health Europe, 2026 Background: We lack data about the early evolution of lung pathophysiology in infants developing moderate-to-severe broncho-pulmonary dysplasia (msBPD). We aimed to describe lung aeration and gas exchange during the early phase of msBPD development and identify the critical moments at which they change. Methods: ratios. msBPD was defined using NIH-2001, NICHD-2018 and Jensen definitions. Findings: < 0.001) with a peak at 26 days. Interpretation: Patients who develop msBPD consistently demonstrate early and typical pathophysiological phenotypes regardless of the BPD definition. These data highlight critical moments in the development of msBPD and are not captured by currently available BPD definitions. Funding: Only institutional funding to support the author's working time was used.
Early prediction of bronchopulmonary dysplasia by urinary metabolomics: a case–control study Luca Bonadies, Serena Calgaro, Matteo Stocchero, Paola Pirillo, Gabriele Poloniato, Lorenzo Zanetto, Laura Moschino, Giuseppe Giordano, Eugenio Baraldi Thorax, 2026 Objective Bronchopulmonary dysplasia (BPD), the most frequent complication of extreme preterm birth, lacks not only of a comprehensive definition but also of effective treatments and predictive tools. Metabolomics is a valuable tool to unravel the underlying pathogenetic pathways of diseases and identify possible early markers. The objective of this study was to find metabolic signatures of subsequent BPD development, defined and stratified as per Jobe and Bancalari 2001 NHICD Consensus. Methods In this observational case–control study, we initially enrolled 161 very preterm unmatched infants, collected their urine samples during the first 24 hours of life and performed metabolomics evaluations on these samples. Patients were then followed until 36 weeks postmenstrual age. To reduce the influence of gestational age and other confounders on metabolome, we applied a nested case–control matching procedure that allowed the selection of 25 BPD cases and 25 non-BPD controls. Results Multivariate and univariate data analysis led to the recognition of 17 metabolites related to BPD development in the first day of life, of which three were identified: L-Glutamic acid (p value=0.038), o-Hydroxyphenylacetic acid (p=0.039), L-Homoserine (p value=0.020). Some of these metabolites are known to play a role in the protection against oxidative stress and/or inflammatory response, two of the most known factors involved in BPD pathogenesis. In particular, L-Glutamic acid and its ionic form glutamate were increased in infants developing BPD suggesting a role as promising marker of the disease. Conclusions Our findings pave the way to better characterise early origin of BPD from a metabolic point of view towards a better biological framework of the disease and, eventually, its prediction and possible new treatments.
Reply: Lung organoids: a new frontier in neonatology and paediatric respiratory medicine Lorenzo Zanetto, Luca Bonadies, Raquel Moll-Diaz, Jeffrey Beekman, Maurizio Muraca, Michela Pozzobon, Eugenio Baraldi European Respiratory Review, 2026 <title>Extract</title> We would like to thank P. Das and V. Bhandari for their interest in and comments on our recently published review on lung organoids [1]. We welcome the opportunity offered by their thoughtful correspondence to further elaborate on specific aspects of organoid-based research that could not be addressed in our original review, which primarily focused on the strengths and limitations of the model itself. Overall, the authors' comments highlight several challenges associated with research involving substances of human origin (SoHO), including ethical, logistical and biological concerns.
Randomised al.Phase 2b trial of rhIGF-1/rhIGFBP-3 (OHB-607) for bronchopulmonary dysplasia prevention in preterm neonates: study protocol Eugenio Baraldi, Daniele De Luca, Luca Bonadies, Shinya Hirano, Satoshi Kusuda, Eduardo Bancalari, Rangasamy Ramanathan, Norman Barton, Alecia Nickless, Jane Lee, Navdeep Mahajan, Victoria Niklas BMJ Paediatrics Open, 2026 Introduction Bronchopulmonary dysplasia (BPD) is the most common complication of prematurity, characterised by impaired alveolarisation and pulmonary vascular development. BPD has been associated with an increased risk of respiratory morbidity, neurodevelopmental impairment and death, intensifying a lifelong health and economic burden. The current standard of neonatal care is primarily supportive, with no approved therapies to restore lung development, promote maturation and lung growth or prevent long-term sequelae. Therefore, there is a critical unmet need for novel interventions, particularly in high-risk, extremely premature (EP) infants. In EP infants, serum insulin-like growth factor-1 (IGF-1) levels decrease rapidly and remain low for the first weeks after birth relative to the corresponding foetal levels in utero. Methods and analysis OHB-607, a recombinant human IGF-1 combined with its binding protein-3, may replenish IGF-1 during this period of deficiency and support lung and vascular maturation. OHB-607 is being investigated as a first-line therapy to prevent severe BPD in EP infants in a Phase 2b, multicentre, open-label, randomised trial. Here, we present the Phase 2b study protocol. Target enrolment is 338 EP infants. To mimic physiological IGF-1 levels in utero, OHB-607 will be administered starting within 24 hours of birth until 29 +6 weeks postmenstrual age (PMA) via continuous intravenous infusion. The primary endpoint is the incidence of severe BPD, based on the modified National Institute of Child Health and Human Development criteria, or death by 36 weeks PMA. Key secondary endpoints include weaning from respiratory support at 12 months corrected age and BPD severity (Grade 2/3) by the 2019 Neonatal Research Network definition. Other secondary endpoints include other complications of prematurity, neurodevelopmental outcomes and family and infant well-being and social functioning through 24 months’ corrected age, and pharmacokinetic and dynamic impact of OHB-607 on the multisystem consequences of prematurity, and overall safety in modifying the natural history of BPD and its consequences. Ethics and dissemination Findings will be disseminated via local and international congresses and publications. Trial registration number ClinicalTrials.gov ( NCT03253263 ), Clinicaltrialsregister.eu (EudraCT: 2018-001393-16), Euclinicaltrials.eu (EUCT: 2024-515914-41-00) and Pmda.go.jp (PMDA: jRCT2031240339).
Do newborns detect prosodic violations in an unfamiliar language at birth? Caterina Marino, Jessica Gemignani, Marcela Peña, Anna Martinez-Alvarez, Luca Bonadies, Eugenio Baraldi, Judit Gervain Brain and Language, 2025 • The ability to process prosodic information is present already at birth. • This early prosodic perception is crucial for later language acquisition. • We tested infants exposed prenatally to Italian with French stimuli. • We found that they discriminate between standard and deviant French prosody. • The timing and localization of brain responses differ from those of French newborns. Experience with language starts prenatally, as the intrauterine environment allows speech prosody to get through. Martinez-Alvarez and colleagues (2023) demonstrated that newborns detect utterance-level prosodic violations in the language they heard prenatally, French. It remains unknown, however, whether this discrimination ability requires prenatal experience with a given language or whether newborns have an early sensitivity to the shapes of prosodic contours that extends beyond prenatal experience. To this purpose, we tested infants exposed prenatally to Italian with the French stimuli of Martinez-Alvarez et al. (2023) , and we measured their brain responses with fNIRS. We found that Italian-exposed newborns discriminate between standard and deviant prosodic contours in French, activating right hemispheric areas specialized for the processing of prosody in adults. However, the time course and the localization of the effect were different from those found in French newborns. This suggests that an early sensitivity to prosodic contours may be modulated by prenatal experience at birth.
External Validation of a Multivariate Model for Targeted Surfactant Replacement Francesco Raimondi, Pasquale Dolce, Claudio Veropalumbo, Enrico Sierchio, Rebeca Gregorio Hernandez, Javier Rodriguez Fanjul, Fabio Meneghin, Roberto Raschetti, Luca Bonadies, Iuri Corsini, Almudena Alonso Ojembarrena, Serena Salomè, Lorena Rodeño Fernandez, Manuel Sanchez Luna, Gianluca Lista, Fabio Mosca, Carlo Dani, Eugenio Baraldi, Lucio Giordano, Peter G Davis, Letizia Capasso Neonatology, 2024
Optimised versus standard dosing of vancomycin in infants with Gram-positive sepsis (NeoVanc): a multicentre, randomised, open-label, phase 2b, non-inferiority trial Louise F Hill, Michelle N Clements, Mark A Turner, Daniele Donà, Irja Lutsar, Evelyne Jacqz-Aigrain, Paul T Heath, Emmanuel Roilides, Louise Rawcliffe, Clara Alonso-Diaz, Eugenio Baraldi, Andrea Dotta, Mari-Liis Ilmoja, Ajit Mahaveer, Tuuli Metsvaht, George Mitsiakos, Vassiliki Papaevangelou, Kosmas Sarafidis, A Sarah Walker, Michael Sharland, Louise F Hill, Michelle Clements, Mark A Turner, Daniele Donà, Irja Lutsar, Evelyne Jacqz-Aigrain, Paul T Heath, Emmanuel Roilides, Louise Rawcliffe, Basma Bafadal, Ana Alarcon Allen, Clara Alonso-Diaz, Fani Anatolitou, Eugenio Baraldi, Antonio Del Vecchio, Andrea Dotta, Mario Giuffrè, Mari-Liis Ilmoja, Korina Karachristou, Ajit Mahaveer, Paolo Manzoni, Stefano Martinelli, Tuuli Metsvaht, George Mitsiakos, Paul Moriarty, Angeliki Nika, Vana Papaevangelou, Charles Roehr, Laura Sanchez Alcobendas, Kosmas Sarafidis, Tania Siahanidou, Chryssoula Tzialla, Luca Bonadies, Nicola Booth, Paola Catalina Morales-Betancourt, Malaika Cordeiro, Concha de Alba Romero, Javier de la Cruz, Maia De Luca, Daniele Farina, Caterina Franco, Dimitra Gialamprinou, Maarja Hallik, Laura Ilardi, Vincenzo Insinga, Elias Iosifidis, Riste Kalamees, Angeliki Kontou, Zoltan Molnar, Eirini Nikaina, Chryssoula Petropoulou, Mar Reyné, Kassandra Tataropoulou, Pinelopi Triantafyllidou, Adamantios Vontzalidis, A Sarah Walker, Mike Sharland Lancet Child and Adolescent Health, 2022
