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Open research questions in Neonatal Respiratory Health Research

750 gap statements mined from Neonatal Respiratory Health Research papers in our 7.9M-paper local library, which holds 3,080 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.

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What the literature leaves open

  • Despite decades of research, many surfactant trials have been limited by heterogeneous inclusion criteria, variable dosing/reporting, inconsistent co-interventions (e.g., ventilation strategies), and non-standardized outcomes, which reduces comparability and certainty of effect estimates.

    Surfactant therapy in neonatal care: advances, challenges, and practical considerations · 2026 · DOI

  • The use of lung recruitment with equivalent pressures and NM interface in an understudied subgroup of preterm neonates not only addresses the lacunae in the current literature on NHFOV use, but also provides a rigorous comparison between the two modalities.

    Non-invasive high-frequency oscillation ventilation versus nasal CPAP as primary respiratory support in preterm neonates ≥ 30 weeks with RDS: a non-inferiority randomized controlled trial · 2026 · DOI

  • In this population, the balance between potential benefits of avoiding mechanical ventilation and procedural risks, including physiological instability and technical challenges, remains unclear. Given the limited evidence base, routine use of LISA/ MIST in LPT and term neonates currently cannot be recommended.

    Surfactant administration in late preterm and term neonates: is LISA ready for routine use? · 2026 · DOI

  • Study flowchart nonvigorous IUGR neonates who already exhibit subclinical myocardial dysfunction and increased cerebral blood flow due to fetal brain-sparing remains uncertain.

    Hemodynamic effects of umbilical cord milking versus early cord clamping in nonvigorous intrauterine growth restricted neonates: a randomized controlled trial · 2026 · DOI

  • Future trials should be adequately powered and use streamlined, clinically adaptable protocols. Simplified designs directly comparing odorized versus sham air pulses may improve recruitment and feasibility. Predefined subgroup analyses should evaluate the influence of respiratory support, apnea phenotype, baseline apnea burden, postnatal maturational stage, autonomic profile, and concomitant treatments.

    Automated intermittent olfactory stimulation to reduce apnea in preterm infants: results of the PREMODEUR randomized clinical trial · 2026 · DOI

  • The optimal level of distending pressure during DR stabilisation remains uncertain, despite CPAP being the cornerstone of respiratory support for spontaneously breathing preterm infants.

    Initial CPAP of 5 versus 8 cmH2O during delivery room stabilisation of very preterm infants: the PHILODENDROOM pilot randomised trial · 2026 · DOI

  • Airway manipulation using a laryngoscope remains a key limitation of both the InSurE and LISA/MIST approaches, potentially triggering physiological instability and stress responses.

    Non-Invasive Surfactant Administration in Preterm Infants · 2026 · DOI

  • Major gaps persist, including limited randomized data, uncertainty regarding optimal timing of intervention, and a lack of validated predictors of treatment response. Future priorities include multicenter trials, standardized phenotyping, integration of advanced imaging and biomarkers, and longitudinal studies to better define outcomes.

    Physiology-Based Diagnosis and Management of Bronchopulmonary Dysplasia Associated Pulmonary Hypertension (BPD-PH) · 2026 · DOI

  • It also provides the first UK specific description of current approaches to feeding infants on nCPAP and HFNC, addressing an important gap in the literature and offering context specific insights to inform clinical practice.

    Survey of Oral Feeding Practices Amongst Health Care Professionals for Infants Receiving Nasal Continuous-Positive Airway Pressure (nCPAP) and High Flow Nasal Canula (HFNC) Respiratory Support in the United Kingdom (UK) · 2026 · DOI

  • These findings indicate that admission complete blood count parameters alone are insufficient to identify early surfactant administration and should not replace direct respiratory and clinical indicators in treatment decisions.

    Association of Complete Blood Count Parameters and Systemic Inflammatory Indices with Early Surfactant Administration in Preterm Infants · 2026 · DOI

  • Future trials should not exclude infants of the smallest gestational ages, should compare modalities at equivalent MAPs to disentangle the effects of cyclic pressure application from those of higher distending pressure, and should systematically assess the impact of synchronization on safety and efficacy, given the differential outcomes observed with SNIPPV versus non-synchronized NIPPV.

    Nasal high-frequency oscillatory ventilation as primary respiratory support in preterm infants with respiratory distress syndrome: current evidence and clinical implications · 2026 · DOI

  • Although adverse short and long-term respiratory outcomes in preterm children after NICU discharge are well known, there are only limited data on specific diagnoses, and quantification of HCRU and economic costs beyond the NICU course.

    Long-term clinical and economic outcomes post birth hospitalization in preterm infants with neonatal respiratory distress syndrome: a US real-world retrospective cohort study · 2026 · DOI

  • The net benefit of ACS administration before planned caesarean birth remains unclear; however, there was evidence of potential neonatal harm when birth occurred after 37 weeks' gestation.

    Neonatal outcomes following antenatal corticosteroid administration before planned caesarean birth at late preterm or early term (36–38 weeks’ gestation): a retrospective cohort study · 2026 · DOI

  • Future studies should consider expanding the sample size and conducting multicenter studies to enhance the external validity of our findings. The exact mechanism linking intraventricular hemorrhage and ROP remains unclear; however, some studies suggest that both intraventricular hemorrhage and ROP share similar characteristics with pathological changes related to immature blood vessels and an unstable oxygen supply.

    Are the Risk Factors for Bronchopulmonary Dysplasia and Retinopathy of Prematurity in Very Low-Birth-Weight Infants the Same? · 2025 · DOI

  • Bronchopulmonary dysplasia (BPD) associated pulmonary hypertension (BPD-PH) is the most severe endotype of BPD; there is insufficient evidence to support the optimal screening strategy in at-risk infants.

    Screening for pulmonary hypertension in preterm infants with bronchopulmonary dysplasia: when, how often and does it matter? · 2025 · DOI

  • Data on term neonates is lacking with only one study having looked at neonates born >37 weeks GA.

    The Babyccino: The Role of Caffeine in the Prevention of Acute Kidney Injury in Neonates—A Literature Review · 2024 · DOI

  • However, it must be clearly stated that solid, real-world clinical evidence demonstrating definitive perioperative benefits is currently lacking.

    Biophysical rationale and emerging clinical perspectives of surfactants in thoracic surgery: a translational review · 2026 · DOI

  • Biomarkers of surfactant dysfunction are not standardized, optimal delivery strategies are not established, and the clinical utility of biomarkerenriched surfactant trials remains to be demonstrated.

    Phenotype-Guided Surfactant Therapy in ARDS: From Failed Replacement to Targeted Biological Intervention, Narrative Review · 2026 · DOI

  • Ketamine infusion use in extremely preterm infants with sBPD is increasing, particularly in recent years and among those with the highest Its evolving role as a rescue or an adjunctive sedative highlights both its potential utility and the current gaps in evidence.

    Temporal trends and clinical factors associated with ketamine infusion in hospitalized infants with bronchopulmonary dysplasia · 2026 · DOI

  • Neonatal respiratory support devices now have algorithms for automated adjustment of oxygen concentration (fraction of inspired oxygen (FiO 2)) in response to oxygen saturation (SpO 2) disturbances, but their performance has not been systematically examined.

    Neonatal automated oxygen titration algorithms: response characteristics and performance · 2026 · DOI

  • Future research should investigate how integrating NICU diaries into routine care could support and enhance FCC practices.

    A Closer Look at Parental Narratives: A Qualitative Analysis of Parental Entries in Neonatal Research Diaries of Preterm Infants Participating in the REPORT-BPD Feasibility Study · 2025 · DOI

  • Optimal timing of continuous positive airway pressure (CPAP) cessation in preterm infants remains undetermined.

    Extended CPAP or low-flow nasal cannula for intermittent hypoxaemia in preterm infants: a 24-hour randomised clinical trial · 2024 · DOI

  • Long-term follow-up imaging beyond the neonatal hospitalization was not systematically available for this cohort: no standardized post-discharge imaging protocol was in place, and the limited incidental imaging obtained for other clinical indications in a small number of patients was neither uniform in modality nor in timing, precluding any meaningful assessment of the long-term morphological evolution of cystic…

    Cystic lung lesions secondary to persistent pulmonary interstitial emphysema in preterm infants: imaging features and clinical course · 2026 · DOI

  • Clinical outcomes vary widely across the BPD severity spectrum, and higher-grade BPD is strongly associated increased neonatal mortality and neurodevelopmental…

    The predictive value of cord blood 25-hydroxyvitamin D and vitamin A levels for bronchopulmonary dysplasia in preterm infants · 2026 · DOI

  • The use of prophylactic hydrocortisone varied widely across centers, with only 60% reporting systematic or selective use.

    Hydrocortisone use in France: current practices in 2026 · 2026 · DOI

Most-cited papers in Neonatal Respiratory Health Research

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Open questions raised by papers listed on this page include: (1) In this population, the balance between potential benefits of avoiding mechanical ventilation and procedural risks, including physiological instability and technical challenges, remains unclear (“Surfactant administration in late preterm and term neonates: is LISA ready for…”, 2026); (2) Future trials should be adequately powered and use streamlined, clinically adaptable protocols (“Automated intermittent olfactory stimulation to reduce apnea in preterm…”, 2026); (3) Major gaps persist, including limited randomized data, uncertainty regarding optimal timing of intervention, and a lack of validated predictors of treatment response (“Physiology-Based Diagnosis and Management of Bronchopulmonary Dysplasia…”, 2026); (4) The net benefit of ACS administration before planned caesarean birth remains unclear; however, there was evidence of potential neonatal harm when birth occurred after 37 weeks' gestation (“Neonatal outcomes following antenatal corticosteroid administration before…”, 2026); (5) Biomarkers of surfactant dysfunction are not standardized, optimal delivery strategies are not established, and the clinical utility of biomarkerenriched surfactant trials remains to be demonstrated (“Phenotype-Guided Surfactant Therapy in ARDS: From Failed Replacement to…”, 2026). 750 gap statements have been mined from Neonatal Respiratory Health Research papers in our 7.9M-paper local library, which holds 3,080 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one, so you can read the original claim in context.

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