OBJECTIVE:To investigate the relationship between umbilical arterial pH (UA-pH), heart rate (HR) and positive pressure ventilation (PPV) at birth. METHODS:A prospective cohort study conducted at Stavanger University Hospital, Norway, June 2019-November 2021. Newborns of gestational age ≥28 weeks were eligible for inclusion. UA-pH was routinely obtained at birth and newborn HR captured using dry-electrode ECG. Relationships were evaluated using linear correlation and logistic regression. UA-pH was categorised as <7.00, 7.00-7.09, 7.10-7.19, with reference group 7.20-7.50. Outcome measures were newborn HR and PPV. RESULTS:Among 3662 newborns the median (quartiles) UA-pH was 7.24 (7.19, 7.29). UA-pH <7.00 was identified in 20 (0.5%), 7.00-7.09 in 140 (3.8%), 7.10-7.19 in 833 (23%), and 7.20-7.50 in 2669 (73%) newborns. There was a weak and clinically insignificant linear correlation between UA-pH and first measured HR at 16 (11, 30) s (r = 0.07, p < 0.001), and no linear correlation with HR at one minute (r = -0.03, p = 0.07). Even among newborns with UA-pH <7.00, only 50% were bradycardic with HR values <100 bpm in the first minute (OR 5.0 (1.9, 12.9), p < 0.001). PPV was provided to 117/3662 (3.2%) of newborns. One-third with UA-pH <7.00 received PPV at birth (OR 21.9 (8.0, 55.4), p < 0.001). Apgar scores were strongly associated with UA-pH. CONCLUSION:There was no linear correlation between UA-pH and HR at one minute. Although HR alone was not a good indicator of acidaemia, low UA-pH is associated with bradycardia and PPV. Apgar scores reflected the degree of birth asphyxia very well. CLINICAL TRIAL REGISTRATION:NCT03849781.
QuestionDoes initiating resuscitation of extremely preterm newborns with a higher level of fraction of inspired oxygen (Fio2; 0.6) reduce risk of death or brain injury compared with a lower Fio2 (0.3)?FindingsThis randomized clinical trial of 1469 infants born at 23 to 28 weeks' gestation in 6 countries found no association between initial Fio2 and death or brain injury at 36 weeks' corrected gestational age (46.9% vs 47.8%).MeaningThere was no difference in risk of brain injury or death after initiating resuscitation with an Fio2 of 0.6 vs 0.3. ImportanceThe most effective initial fraction of inspired oxygen (Fio2) for resuscitating preterm newborns is unknown.ObjectiveTo compare outcomes of newborns born at 23 to 28 weeks' gestation resuscitated with initial Fio2 of 0.6 vs 0.3.Design, Setting, and ParticipantsRandomized clinical trial conducted in 31 maternity hospitals in 6 countries. Consent by waiver was obtained in Australia, certain institutions in India, and Malaysia; prospective informed consent was obtained in certain institutions in India and all institutions in Singapore, Spain, and the US. Infants due at 23 to 28 weeks' gestation were randomized shortly before birth. Those with congenital abnormalities affecting oxygenation, neurodevelopment, or survival were excluded. Randomization was conducted from September 2018 to September 2024, with follow-up expected to close in September 2026.InterventionInfants were randomized (1:1) to receive an initial Fio2 of 0.6 or 0.3; Fio2 was titrated to meet standard targets for oxygen saturation by pulse oximetry in the first 10 minutes or for clinical needs. Clinicians and those assessing outcomes were not blinded to group assignment.Main Outcomes and MeasuresThe primary outcome was death and brain injury at 36 weeks' corrected gestational age; secondary outcomes were the individual components of the primary outcome.ResultsA total of 1641 newborns were randomized. The primary analysis included 728 newborns randomized to receive an Fio2 of 0.6 and 741 to an Fio2 of 0.3 after excluding 172 newborns, mostly for birth after 28 weeks' gestation and transfer to another hospital before birth (54% female). Rates of escalation to Fio2 of 1.0 were similar between the groups (Fio2 of 0.6: 41%; Fio2 of 0.3: 38%). Primary outcome information was ascertained in 1423 newborns (96.9%). Death or brain injury at 36 weeks' corrected gestational age occurred in 330 of 703 newborns (46.9%) assigned to the Fio2 of 0.6 group vs 344 of 720 (47.8%) assigned to the Fio2 of 0.3 group (relative risk, 0.98 [95% CI, 0.89-1.09]).Conclusions and RelevanceInitiating resuscitation of preterm infants with Fio2 of 0.6 vs 0.3 did not affect the risk of death or brain injury by 36 weeks' corrected gestational age. These results lay a foundation for future trials evaluating the effectiveness and safety of using higher initial Fio2 levels for preterm infant resuscitation.Trial RegistrationANZCTR Identifier: ACTRN12618000879268 This randomized clinical trial compares outcomes of preterm newborns receiving initial resuscitation with a higher level of fraction of inspired oxygen (Fio2; 0.6) compared with a lower Fio2 (0.3).
INTRODUCTION:Bronchopulmonary dysplasia (BPD) is a leading cause of morbidity and mortality in preterm infants. Combining surfactant with budesonide has been proposed to prevent BPD, but results from existing randomised controlled trials (RCTs) are conflicting. Individual participant data meta-analysis (IPD-MA) synthesises raw trial data, increasing precision, improving assessment of data quality and enabling subgroup analyses. This IPD-MA aims to examine the effect of surfactant plus budesonide versus surfactant alone. METHODS:We will systematically search medical databases and trial registers for RCTs enrolling preterm infants born at < 32 weeks' gestation randomised to intratracheal surfactant alone or surfactant plus budesonide. Studies with major quality concerns will be excluded. Risk of bias will be assessed using Cochrane's RoB 2 tool. Two-stage fixed-effects IPD-MA will be performed with co-primary outcomes of all-cause mortality at hospital discharge and BPD at 36 weeks' postmenstrual age. Subgroups will be examined using treatment-covariate interactions. Certainty of evidence will be assessed using GRADE. A nested prospective meta-analysis will also be conducted. The study is preregistered on PROSPERO (CRD42023456941). CONCLUSION:If effective, surfactant plus corticosteroid would be a low-cost addition to standard care to reduce BPD and increase survival. IPD-MA will allow further insight into treatment effects.
Importance:The most effective initial fraction of inspired oxygen (Fio2) for resuscitating preterm newborns is unknown. Objective:To compare outcomes of newborns born at 23 to 28 weeks' gestation resuscitated with initial Fio2 of 0.6 vs 0.3. Design, Setting, and Participants:Randomized clinical trial conducted in 31 maternity hospitals in 6 countries. Consent by waiver was obtained in Australia, certain institutions in India, and Malaysia; prospective informed consent was obtained in certain institutions in India and all institutions in Singapore, Spain, and the US. Infants due at 23 to 28 weeks' gestation were randomized shortly before birth. Those with congenital abnormalities affecting oxygenation, neurodevelopment, or survival were excluded. Randomization was conducted from September 2018 to September 2024, with follow-up expected to close in September 2026. Intervention:Infants were randomized (1:1) to receive an initial Fio2 of 0.6 or 0.3; Fio2 was titrated to meet standard targets for oxygen saturation by pulse oximetry in the first 10 minutes or for clinical needs. Clinicians and those assessing outcomes were not blinded to group assignment. Main Outcomes and Measures:The primary outcome was death and brain injury at 36 weeks' corrected gestational age; secondary outcomes were the individual components of the primary outcome. Results:A total of 1641 newborns were randomized. The primary analysis included 728 newborns randomized to receive an Fio2 of 0.6 and 741 to an Fio2 of 0.3 after excluding 172 newborns, mostly for birth after 28 weeks' gestation and transfer to another hospital before birth (54% female). Rates of escalation to Fio2 of 1.0 were similar between the groups (Fio2 of 0.6: 41%; Fio2 of 0.3: 38%). Primary outcome information was ascertained in 1423 newborns (96.9%). Death or brain injury at 36 weeks' corrected gestational age occurred in 330 of 703 newborns (46.9%) assigned to the Fio2 of 0.6 group vs 344 of 720 (47.8%) assigned to the Fio2 of 0.3 group (relative risk, 0.98 [95% CI, 0.89-1.09]). Conclusions and Relevance:Initiating resuscitation of preterm infants with Fio2 of 0.6 vs 0.3 did not affect the risk of death or brain injury by 36 weeks' corrected gestational age. These results lay a foundation for future trials evaluating the effectiveness and safety of using higher initial Fio2 levels for preterm infant resuscitation. Trial Registration:ANZCTR Identifier: ACTRN12618000879268.
BACKGROUND:Concentrations of the long-chain polyunsaturated fatty acids, in particular, the ω-3 (n-3) fatty acid DHA and the ω-6 fatty acid arachidonic acid (AA), decrease in infant blood during the first days after very preterm birth. OBJECTIVES:This study aimed to explore factors associated with blood DHA and AA concentrations of very preterm infants receiving standard care, in the days following birth. METHODS:We examined the fatty acid composition of whole blood samples collected on cards at 0-6 d after birth, from a cross-sectional study of 1174 infants born <29 weeks of gestation in Australia, New Zealand, and Singapore. RESULTS:Considerable variation was observed in the proportions of blood AA (1.4%-18.0%) and DHA (0.4%-5.7%) concentrations. Infant blood DHA status was not associated with gestational age at birth, but AA was lower by 0.11% for each week of gestation (95% CI: -0.07%, 0.15%). There was an inverse relationship between age of sampling after birth and DHA (0.07% lower per day; 95% CI: 0.04%, 0.09%) and AA (0.09% lower; 95% CI: 0.04%, 0.14%). A concomitant positive relationship was observed between days after birth and the fatty acids present in the intravenous lipid emulsion administered: ω-6 linoleic acid (range: 2.1%-35.1%) and ω-9 oleic acid (range: 12.2%-52.9%). CONCLUSIONS:Preterm infants whose blood was sampled later after birth have lower DHA and AA status relative to those sampled earlier after birth; samples taken at later timepoints are concurrently higher in the fatty acids of linoleic acid and oleic acid, which are the major compositional components of intravenous lipid emulsions routinely administered to preterm infants. The results support calls to develop intravenous feeds closely matching the fatty acid composition of infant blood at birth. The N3RO Trial is registered at the Australian New Zealand Clinical Trial Registry as ACTRN12612000503820 (https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12612000503820).
BACKGROUND:Delivery room trials face ethical and logistical enrolment challenges, including requirements for prospective, antenatal, parental consent. The Sustained Aeration of Infant Lungs (SAIL) study was a randomised controlled trial of two resuscitation strategies at birth, enrolling infants using both prospective antenatal consent and deferred postnatal (consent-to-continue) pathways. We aimed to compare recruitment and outcomes between SAIL trial centres with deferred consent available versus centres only using prospective antenatal consent. METHOD:This study is a secondary analysis of the data from the open-label, international, multicentre, randomised SAIL trial. Infants born at 23 to less than 27 weeks' gestation at 18 centres across nine countries who were deemed to require intermittent positive pressure ventilation due to inadequate respiratory efforts or bradycardia, had no known major congenital anomalies, and were neither stillborn nor considered to be non-viable by their clinician were eligible for inclusion. Centres were compared by consent mode availability: antenatal consent only versus centres with deferred consent available. The primary outcome was the combined rate of death or bronchopulmonary dysplasia compared between consent type groups. People with lived experience did not contribute to the design or implementation of the SAIL trial. The SAIL trial was registered with ClinicalTrials.gov (NCT02139800). FINDINGS:The SAIL trial recruited 426 infants (222 [52%] were male and 204 [48%] were female) born from 371 mothers (218 [59%] were White) between Aug 27, 2014, and Sept 14, 2017. In 12 centres using only antenatal consent, 197 (41%) of 479 eligible infants were recruited and included in analysis compared with 229 (73%) of 313 eligible infants from six centres where deferred consent was available (with or without antenatal consent; absolute difference 31·78% [95% CI 24·46-39·10; p<0·0001]). Deferred consent was not obtained from 34 (15%) of 225 infants randomly assigned via the deferred pathway, who were excluded from this analysis. Compared with centres using only antenatal consent, infants recruited at deferred consent centres had less exposure to antenatal corticosteroids (166 [84%] of 197 vs 167 [73%] of 229 infants, p=0·012); were more likely to be male (88 [45%] vs 134 [59%], p=0·0065); were heavier (median birthweight 687 g [IQR 558-817] vs 767 g [661-870], p<0·0001); were less likely to be growth restricted (34 [27%] vs 19 [8%], p=0·0075); and less frequently intubated at birth (125 [63%] vs 105 [46%], p=0·0005). The rate of death or bronchopulmonary dysplasia at deferred consent centres was 65% (149/229) versus 57% (113/197) at antenatal consent centres (adjusted relative risk 1·18 [95% CI 0·98-1·42]). INTERPRETATION:Centres where deferred consent was available recruited a higher proportion of eligible infants at high risk who had more morbidities, reflecting a broader, more generalisable sample of the population compared with centres that only recruited using antenatal consent. FUNDING:Eunice Kennedy Shriver National Institute of Child Health and Human Development.
Introduction The safest oxygen levels needed for preterm infant respiratory support at birth are uncertain. We aimed to compare the outcomes of infants up to 286 weeks gestation who had respiratory care initiated at birth with fractional inspired oxygen (FiO2) 0.3 or 0.6, which was adjusted to meet specific oxygen saturations (SpO2).Methods This randomised controlled phase III trial was stratified by (1) site, (2) gestation and (3) multiplicity. Infants between 23+0 to 28+6 weeks gestation were randomised to initial respiratory support with FiO2 0.3 or 0.6, adjusted to meet common SpO2 targets for the first 10 min.Primary outcome Survival to 36 weeks gestation without documented brain injury.Assessments FiO2, SpO2 and heart rate were recorded each minute from delivery for 10 min. Assessments were obtained at baseline, 36 weeks, discharge and at 2 years corrected gestation, along with a parent questionnaire.Statistical analysis plan Assuming 32% of infants would die or survive with brain injury by 36 weeks, 735 infants per arm (1470 total) were needed to detect a risk difference of 8% (25% relative risk reduction), with 10% non-adherence to protocol, 85% β and 5% α.Ethics Approved by the John Hunter Human Research Ethics Committee (2019/ETH/3837) for waiver of consent for all Australian sites for randomised allocation and primary outcome.Conclusion Recruitment started in 2018 and was achieved on 30 September 2024. The Data and Safety Committee review found no major safety concerns at 50% recruitment.Trial registration number ACTRN 12618000879268.
Importance:Effective lung aeration is crucial for successful postnatal transition. Goal targets to achieve lung aeration during positive pressure ventilation have not been established for preterm neonates. Objective:To identify respiratory parameters associated with successful lung aeration during delivery room resuscitation. Design, Setting, and Participants:This multicenter prospective cohort study was conducted from March 2016 to April 2021. The primary population included preterm neonates from 3 centers of 22 weeks to 31 weeks 6 days' gestation with bradycardia who received positive pressure ventilation during resuscitation after birth. An independent population of preterm neonates (24 weeks to 27 weeks 6 days' gestation) in the multicenter Monitoring Neonatal Resuscitation randomized clinical trial served as a confirmatory dataset. Data were analyzed January 2022 to May 2025. Exposures:Rolling means of pressure, inspiratory and expiratory tidal volumes (VTE), and mask leak, as measured with a respiratory function monitor (RFM). Counts of spontaneous breaths between inflations and mask removal instances. Main Outcomes and Measures:The primary outcome was a sustained increase in heart rate to at least 100 beats per minute, indicating effective lung aeration, within the first 10 minutes of resuscitation. Associations between clinical covariates, respiratory parameters, and heart rate increase were examined using cause-specific Cox proportional hazards regression models. Results:There were 132 neonates in the primary dataset (median [IQR] gestation, 26.6 [25.1-29.2] weeks; 67 [50.8%] male) and 115 in the confirmatory dataset (median [IQR] gestation, 26.7 [25.6-27.4] weeks; 65 [56.5%] male). Of 132 primary dataset participants, 125 (94.7%) achieved the primary outcome. Among the measured respiratory parameters, only VTE was associated with an increase in heart rate (adjusted hazard ratio [AHR], 1.10 [95% CI, 1.01-1.20]). The AHR was higher for increases in VTE up to 4 mL/kg (AHR, 1.55 [95% CI, 1.20-2.00]) than for VTEs higher than 4 mL/kg (AHR, 1.04 [95% CI, 0.98-1.10]). These results were consistent with those in the confirmatory dataset: an association for an increase in heart rate with VTE values up to 4 mL/kg (AHR, 1.31 [95% CI, 1.01-1.70]) but not higher than 4 mL/kg (AHR, 1.02 [95% CI, 0.96-1.08]). Other covariates associated with an increase in heart rate included birth weight (per 100 g) (AHR, 1.12 [95% CI, 1.05-1.20]) and mask removal count (AHR, 0.83 [95% CI, 0.70-0.98]). Conclusions and Relevance:This cohort study observed in one neonatal population and confirmed in another that a minimum VTE of 4 mL/kg was associated with successful lung aeration as assessed by an increase in heart rate to at least 100 beats per minute during preterm neonate resuscitation. These results may inform future studies to determine the clinical impact of incorporating data-based targets for delivery room resuscitation of preterm neonates.
BACKGROUND:A total lung ultrasound score (tLUS) is a validated tool to describe parenchymal aeration, evaluate neonatal respiratory distress syndrome (RDS) progression and guide early surfactant replacement. tLUS derives from regional scores (rLUS) from predefined ultrasound views. RESEARCH QUESTION:This paper explores the relative contribution of rLUS to tLUS and their predictive power of surfactant need for RDS, individually and with additional variables. STUDY DESIGN AND METHODS:This was a secondary analysis of multicenter, prospective, observational study. Preterm neonates with RDS were stabilized on nCPAP. Within 2 h of life, we calculated a tLUS (range 0-18) by summing 6 rLUS (using a 0-3 scale on midclavicular, anterior and posterior axillary line views) and the oxygen saturation/inspired oxygen fraction ratio (SatO2/FiO2). The administration of surfactant by a physician masked to the ultrasound results was used as reference test. RESULTS:We enrolled 175 preterm infants. A midclavicular (MC) score ≥ 2 was an early marker of aeration heterogeneity. Prognostic accuracy for surfactant need was high for the left MC score (AUC: 0.86 with sensitivity 0.79 and specificity 0.90) and the right MC score (AUC 0.87 with sensitivity 0.74 and specificity 0.93; optimal Youden cut-off = 2). A combined left + right MC score lead to an AUC: 0.90 (sensitivity 0.82. specificity 0.89; optimal Youden cut-off = 3). A prediction model including gestational age, SatO2/FiO2 and the combined MC score had an AUC 0.95. INTERPRETATION:rLUS are not always uniformly distributed in early RDS. The combined MC score is a simplified rapid and accurate predictor of surfactant replacement (alone or in combination with noninvasive variables) reducing stressful manipulations in first hours of life for preterm neonates.
Background/Objectives: Newborn heart rate is an integral part of resuscitation algorithms, but the impact of ECG monitoring on resuscitative interventions and clinical outcomes has been identified as a knowledge gap. The objective was to evaluate the impact of routine use of dry-electrode ECG in all newborns immediately after birth on time to start positive pressure ventilation (PPV) when indicated. Methods: We conducted a randomized clinical trial from June 2019 to November 2021 at Stavanger University Hospital, Norway. Dry-electrode ECG sensors were applied immediately after birth to all newborns ≥ 34 weeks’ gestation. Randomization determined whether the heart rate display was visible or masked. Time of birth was registered in an observation app. Time to start ventilation was calculated from video recordings. Results: In total, 7343 newborns ≥ 34 weeks’ gestation were enrolled, 4284 in the intervention and 3059 in the control group, and 3.7% and 3.8% received ventilation, respectively. In 171/275 (62%) of the newborns the exact time of birth and a video of the resuscitation were available, for 98 in the intervention and 73 in the control group. Ventilation was provided within 60 s to 44/98 (45%) in the intervention and 24/73 (33%) in the control group, p = 0.12. Time from birth to start of PPV was a median of 66 (44, 102) s in the intervention and 84 (49, 148) s in the control group, p = 0.058. Resuscitated newborns were apneic (74%) or breathing ineffectively (26%) at the start of PPV, and only 36% had a heart rate < 100 beats per minute. Conclusions: The use of dry-electrode ECG heart rate monitoring did not change the proportion of newborns that received ventilation within 60 s after birth, but early termination due to employee protests to video recordings rendered the trial inadequately powered to detect a difference. Breathing status was likely a more important determinant of starting ventilation than bradycardia.
AIM:To identify subgroups of neonates for whom core outcome sets (COS) have been developed, the outcomes that were included and the methods used in their formulation. METHODS:We performed a scoping review and searched databases in April 2025 for published COS. We included COS that reported neonatal outcomes, even when the original interventions targeted pregnant individuals. Methods of COS development and the included outcomes were extracted for descriptive analysis. RESULTS:A total of 363 abstracts were screened and 34 COS studies included for analysis. The most used methods were modified Delphi and Delphi consensus methods, consisting of a median of three rounds and a consensus meeting. Overall, a total of 62 distinct neonatal outcomes were proposed. The five most commonly included outcomes were neonatal mortality, preterm birth, birth weight, need for neonatal intensive care unit admission and neurodevelopment. CONCLUSION:We found that the neonatal core outcome sets had clear heterogeneity in their selected outcomes. Future primary studies and evidence reviews should aim to focus on including important outcomes, when possible, to improve consistency in reporting. PROTOCOL REGISTRATION:Protocol was registered to open science framework and is available from https://osf.io/yngbd/.
BACKGROUND:Up to 10 % of all newborns require assistance to breathe at birth. Although neonatal resuscitation guidelines and educational platforms exist, best practices to implement high-quality neonatal resuscitation care have not been defined. AIM:To establish a Neonatal Global Resuscitation Alliance and develop ten steps to improve outcomes of in-facility neonatal resuscitation across global settings. METHODS:Three-stage iterative consensus-based process: (1) invited input from the neonatal resuscitation community to identify pertinent measures, (2) convened a face-to-face meeting of 28 global neonatal resuscitation content experts to refine consensus steps, (3) presented draft steps and related content to stakeholders; solicited public comment and revised ten steps based on feedback. RESULTS:The consensus-based ten steps include: Implement effective education systems; Ensure team and equipment readiness; Identify high-risk pregnancies and prevent perinatal risks; Respond to every birth; Perform guideline based resuscitation; Deliver guideline based post-resuscitation care; Collect data throughout resuscitation care; Improve quality of resuscitation; Support parent and family well-being; Cultivate a culture of excellence. For each of these steps, key concepts and suggested approaches to put the steps into practice are identified. CONCLUSION:These ten steps to improve outcomes of in-facility neonatal resuscitation represent a clear framework for healthcare professionals, institutions, and policymakers to evaluate and strengthen their readiness, training, and response to newborns who need resuscitation at birth. This consensus-based guidance can be used to optimize in-facility neonatal resuscitation and improve outcomes for newborns worldwide.
Neonatal mortality remains unacceptably high throughout the world. Survival of sick infants in their first month of life has improved over the past six decades. However, many comorbidities persist, with lifelong implications for health. The current ecosystem for research and development of drugs and medical devices to treat neonatal disorders is hindering further improvements to neonatal outcomes, especially infants born preterm or needing critical care. Innovation is lagging, and this is a public health problem characterised by multifactorial challenges in leadership, collaboration, regulation, funding, and commercial viability. The Lancet Child & Adolescent Health Commission on the future of neonatology was created to consider these challenges and design a roadmap of strategies to accelerate research and development that will innovate and improve health care for neonates. We call for regulatory agencies, governments, funders, industry partners, and clinical researchers from diverse medical fields to invest in effective pathways for drug and medical device development and to unite in responsive and dynamic collaborations with diverse patients, families, and advocacy groups whose engagement in clinical research and advocacy can help neonatologists to achieve the best science and health equity for neonates worldwide, now and in the future.
OBJECTIVE:The James Lind Alliance (JLA) Most Premature Babies Priority Setting Partnership aimed to identify the most important areas for research for infants born <25 weeks' gestation. DESIGN:Employing standardised JLA methodology, questions for research were sought from stakeholders via an online survey. Summary questions were formed and checked against existing evidence, with unanswered questions compiled into a second shortlisting survey for prioritisation by stakeholders. A stakeholder consensus workshop was held to determine the top 10 research priorities. PARTICIPANTS:People with lived experience of neonatal intensive care, including parents/carers of preterm infants and adults born preterm, and healthcare professionals caring for preterm infants across Australia, New Zealand and the UK. MAIN OUTCOME MEASURE:The top 10 research priorities for infants born <25 weeks' gestation. RESULTS:From 844 questions received from the initial survey, 81 summary questions were formed, of which 80 were unanswered and included in the second shortlisting survey. The 19 top-ranked questions were taken to the final prioritisation workshop, where the top 10 research priorities were determined by people with lived experience and healthcare professionals. The most important research question identified was 'What can be done in the neonatal intensive care unit to improve long-term health and developmental outcomes?'. Other important areas for research included antenatal interventions and neonatal care at birth, preventing intraventricular haemorrhages, managing pain, postnatal corticosteroid treatment and supporting families. CONCLUSIONS:This study identified the most important areas of research for infants born <25 weeks' gestation, as determined jointly by stakeholders. These findings should be used to guide future research and funding aimed at improving meaningful outcomes for these infants and their families.