COHESION: a core outcome set for the treatment of neonatal encephalopathy.

BACKGROUND: Heterogeneity in outcomes reported in trials of interventions for the treatment of neonatal encephalopathy (NE) makes evaluating the effectiveness of treatments difficult. Developing a core outcome set for NE treatment would enable researchers to measure and report the same outcomes in future trials. This would minimise waste, ensure relevant outcomes are measured and enable evidence synthesis. Therefore, we aimed to develop a core outcome set for treating NE. METHODS: Outcomes identified from a systematic review of the literature and interviews with parents were prioritised by stakeholders (n = 99 parents/caregivers, n = 101 healthcare providers, and n = 22 researchers/ academics) in online Delphi surveys. Agreement on the outcomes was achieved at online consensus meetings attended by n = 10 parents, n = 18 healthcare providers, and n = 13 researchers/ academics. RESULTS: Seven outcomes were included in the final core outcome set: survival; brain injury on imaging; neurological status at discharge; cerebral palsy; general cognitive ability; quality of life of the child, and adverse events related to treatment. CONCLUSION: We developed a core outcome set for the treatment of NE. This will allow future trials to measure and report the same outcomes and ensure results can be compared. Future work should identify how best to measure the COS. IMPACT: We have identified seven outcomes that should be measured and reported in all studies for the treatment of neonatal encephalopathy. Previously, a core outcome set for neonatal encephalopathy treatments did not exist. This will help to reduce heterogeneity in outcomes reported in clinical trials and other studies, and help researchers identify the best treatments for neonatal encephalopathy.

Neonatal encephalopathy: a systematic review of reported treatment outcomes.

BACKGROUND: Neonatal encephalopathy (NE) is a multi-organ condition potentially leading to death or long-term neurodisability. Therapeutic hypothermia is the standard treatment for NE; however, long-term impairments remain common. Studies of new treatments for NE often measure and report different outcomes. Core outcome sets (COSs), a minimum set of outcomes to be measured and reported in all studies for a condition, address this problem. This paper aimed to identify outcomes reported (primary, secondary, adverse events and other reported outcomes) in (1) randomised trials and (2) systematic reviews of randomised trials of interventions for the treatment of NE in the process of developing a COS for interventions for the treatment of NE. METHODS: We completed a systematic search for outcomes used to evaluate treatments for NE using MEDLINE, Embase, Cochrane CENTRAL, the Cochrane Database of Systematic Reviews and the WHO International Clinical Trials Registry Platform. Two reviewers screened all included articles independently. Outcomes were extracted verbatim, similar outcomes were grouped and outcome domains were developed. RESULTS: 386 outcomes were reported in 116 papers, from 85 studies. Outcomes were categorised into 18 domains. No outcome was reported by all studies, a single study reported 11 outcomes and it was not explicitly stated that outcomes had input from parents. DISCUSSION: Heterogeneity in reported outcomes means that synthesis of studies evaluating new treatments for NE remains difficult. A COS, that includes parental/family input, is needed to ensure consistency in measuring and reporting outcomes, and to enable comparison of randomised trials.

Developments in the Design, Conduct, and Reporting of Child Health Trials.

To identify priority areas to improve the design, conduct, and reporting of pediatric clinical trials, the international expert network, Standards for Research (StaR) in Child Health, was assembled and published the first 6 Standards in Pediatrics in 2012. After a recent review summarizing the 247 publications by StaR Child Health authors that highlight research practices that add value and reduce research "waste," the current review assesses the progress in key child health trial methods areas: consent and recruitment, containing risk of bias, roles of data monitoring committees, appropriate sample size calculations, outcome selection and measurement, and age groups for pediatric trials. Although meaningful change has occurred within the child health research ecosystem, measurable progress is still disappointingly slow. In this context, we identify and review emerging trends that will advance the agenda of increased clinical usefulness of pediatric trials, including patient and public engagement, Bayesian statistical approaches, adaptive designs, and platform trials. We explore how implementation science approaches could be applied to effect measurable improvements in the design, conducted, and reporting of child health research.

How to reach agreement: the impact of different analytical approaches to Delphi process results in core outcomes set development.

BACKGROUND: Core outcomes sets are increasingly used to define research outcomes that are most important for a condition. Different consensus methods are used in the development of core outcomes sets; the most common is the Delphi process. Delphi methodology is increasingly standardised for core outcomes set development, but uncertainties remain. We aimed to empirically test how the use of different summary statistics and consensus criteria impact Delphi process results. METHODS: Results from two unrelated child health Delphi processes were analysed. Outcomes were ranked by mean, median, or rate of exceedance, and then pairwise comparisons were undertaken to analyse whether the rankings were similar. The correlation coefficient for each comparison was calculated, and Bland-Altman plots produced. Youden's index was used to assess how well the outcomes ranked highest by each summary statistic matched the final core outcomes sets. Consensus criteria identified in a review of published Delphi processes were applied to the results of the two child-health Delphi processes. The size of the consensus sets produced by different criteria was compared, and Youden's index was used to assess how well the outcomes that met different criteria matched the final core outcomes sets. RESULTS: Pairwise comparisons of different summary statistics produced similar correlation coefficients. Bland-Altman plots showed that comparisons involving ranked medians had wider variation in the ranking. No difference in Youden's index for the summary statistics was found. Different consensus criteria produced widely different sets of consensus outcomes (range: 5-44 included outcomes). They also showed differing abilities to identify core outcomes (Youden's index range: 0.32-0.92). The choice of consensus criteria had a large impact on Delphi results. DISCUSSION: The use of different summary statistics is unlikely to affect how outcomes are ranked during a Delphi process: mean, median, and rates of exceedance produce similar results. Different consensus criteria have a large impact on resultant consensus outcomes and potentially on subsequent core outcomes sets: our results confirm the importance of adhering to pre-specified consensus criteria.

National priority setting partnership using a Delphi consensus process to develop neonatal research questions suitable for practice-changing randomised trials in the UK.

BACKGROUND: The provision of neonatal care is variable and commonly lacks adequate evidence base; strategic development of methodologically robust clinical trials is needed to improve outcomes and maximise research resources. Historically, neonatal research topics have been selected by researchers; prioritisation processes involving wider stakeholder groups have generally identified research themes rather than specific questions amenable to interventional trials. OBJECTIVE: To involve stakeholders including parents, healthcare professionals and researchers to identify and prioritise research questions suitable for answering in neonatal interventional trials in the UK. DESIGN: Research questions were submitted by stakeholders in population, intervention, comparison, outcome format through an online platform. Questions were reviewed by a representative steering group; duplicates and previously answered questions were removed. Eligible questions were entered into a three-round online Delphi survey for prioritisation by all stakeholder groups. PARTICIPANTS: One hundred and eight respondents submitted research questions for consideration; 144 participants completed round one of the Delphi survey, 106 completed all three rounds. RESULTS: Two hundred and sixty-five research questions were submitted and after steering group review, 186 entered into the Delphi survey. The top five ranked research questions related to breast milk fortification, intact cord resuscitation, timing of surgical intervention in necrotising enterocolitis, therapeutic hypothermia for mild hypoxic ischaemic encephalopathy and non-invasive respiratory support. CONCLUSIONS: We have identified and prioritised research questions suitable for practice-changing interventional trials in neonatal medicine in the UK at the present time. Trials targeting these uncertainties have potential to reduce research waste and improve neonatal care.

Multi-Round versus Real-Time Delphi survey approach for achieving consensus in the COHESION core outcome set: a randomised trial.

BACKGROUND: Delphi surveys are commonly used to prioritise critical outcomes in core outcome set (COS) development. This trial aims to compare a three-round (Multi-Round) Delphi (MRD) with a Real-Time Delphi (RTD) in the prioritisation of outcomes for inclusion in a COS for neonatal encephalopathy treatments and explore whether 'feedback', 'iteration', and 'initial condition' effects may occur in the two survey methods. METHODS: We recruited 269 participants (parents/caregivers, healthcare providers and researchers/academics) of which 222 were randomised to either the MRD or the RTD. We investigated the outcomes prioritised in each survey and the 'feedback', 'iteration', and 'initial condition' effects to identify differences between the two survey methods. RESULTS: In the RTD, n = 92 participants (83%) fully completed the survey. In the MRD, n = 60 participants (54%) completed all three rounds. Of the 92 outcomes presented, 26 (28%) were prioritised differently between the RTD and MRD. Significantly fewer participants amended their scores when shown stakeholder responses in the RTD compared to the MRD ('feedback effect'). The 'iteration effect' analysis found most experts appeared satisfied with their initial ratings in the RTD and did not amend their scores following stakeholder response feedback. Where they did amend their scores, ratings were amended substantially, suggesting greater convergence. Variance in scores reduced with subsequent rounds of the MRD ('iteration effect'). Whilst most participants did not change their initial scores in the RTD, of those that did, later recruits tended to align their final score more closely to the group mean final score than earlier recruits (an 'initial condition' effect). CONCLUSION: The feedback effect differed between the two Delphi methods but the magnitude of this difference was small and likely due to the large number of observations rather than because of a meaningfully large difference. It did not appear to be advantageous to require participants to engage in three rounds of a survey due to the low change in scores. Larger drop-out through successive rounds in the MRD, together with a lesser convergence of scores and longer time to completion, indicate considerable benefits of the RTD approach. TRIAL REGISTRATION: NCT04471103. Registered on 14 July 2020.

Heterogeneity and Gaps in Reporting Primary Outcomes From Neonatal Trials.

OBJECTIVES: Clear outcome reporting in clinical trials facilitates accurate interpretation and application of findings and improves evidence-informed decision-making. Standardized core outcomes for reporting neonatal trials have been developed, but little is known about how primary outcomes are reported in neonatal trials. Our aim was to identify strengths and weaknesses of primary outcome reporting in recent neonatal trials. METHODS: Neonatal trials including ≥100 participants/arm published between 2015 and 2020 with at least 1 primary outcome from a neonatal core outcome set were eligible. Raters recruited from Cochrane Neonatal were trained to evaluate the trials' primary outcome reporting completeness using relevant items from Consolidated Standards of Reporting Trials 2010 and Consolidated Standards of Reporting Trials-Outcomes 2022 pertaining to the reporting of the definition, selection, measurement, analysis, and interpretation of primary trial outcomes. All trial reports were assessed by 3 raters. Assessments and discrepancies between raters were analyzed. RESULTS: Outcome-reporting evaluations were completed for 36 included neonatal trials by 39 raters. Levels of outcome reporting completeness were highly variable. All trials fully reported the primary outcome measurement domain, statistical methods used to compare treatment groups, and participant flow. Yet, only 28% of trials fully reported on minimal important difference, 24% on outcome data missingness, 66% on blinding of the outcome assessor, and 42% on handling of outcome multiplicity. CONCLUSIONS: Primary outcome reporting in neonatal trials often lacks key information needed for interpretability of results, knowledge synthesis, and evidence-informed decision-making in neonatology. Use of existing outcome-reporting guidelines by trialists, journals, and peer reviewers will enhance transparent reporting of neonatal trials.

Strengthening Reporting of Neonatal Trials.

BACKGROUND AND OBJECTIVES: There is variability in the selection and reporting of outcomes in neonatal trials with key information frequently omitted. This can impact applicability of trial findings to clinicians, families, and caregivers, and impair evidence synthesis. The Neonatal Core Outcomes Set describes outcomes agreed as clinically important that should be assessed in all neonatal trials, and Consolidated Standards of Reporting Trials (CONSORT)-Outcomes 2022 is a new, harmonized, evidence-based reporting guideline for trial outcomes. We reviewed published trials using CONSORT-Outcomes 2022 guidance to identify exemplars of neonatal core outcome reporting to strengthen description of outcomes in future trial publications. METHODS: Neonatal trials including >100 participants per arm published between 2015 to 2020 with a primary outcome included in the Neonatal Core Outcome Set were identified. Primary outcome reporting was reviewed using CONSORT 2010 and CONSORT-Outcomes 2022 guidelines by assessors recruited from Cochrane Neonatal. Examples of clear and complete outcome reporting were identified with verbatim text extracted from trial reports. RESULTS: Thirty-six trials were reviewed by 39 assessors. Examples of good reporting for CONSORT 2010 and CONSORT-Outcomes 2022 criteria were identified and subdivided into 3 outcome categories: "survival," "short-term neonatal complications," and "long-term developmental outcomes" depending on the core outcomes to which they relate. These examples are presented to strengthen future research reporting. CONCLUSIONS: We have identified examples of good trial outcome reporting. These illustrate how important neonatal outcomes should be reported to meet the CONSORT 2010 and CONSORT-Outcomes 2022 guidelines. Emulating these examples will improve the transmission of information relating to outcomes and reduce associated research waste.

Nutrition for the micro preemie: Beyond milk.

Nutritional support is a fundamental component of the care of the extremely preterm infant, including the "micro preemie" (here defined as a baby born weighing less than 500 g), but goes beyond considerations of milk as a food. This is because milk from an infant's own mother, unlike currently available substitutes, additionally provides invaluable non-nutritive benefits. Nutritional support requires suitable devices or techniques to administer nutrients enterally or intravenously, products shown to be safe in preterm populations, and efficacy demonstrated in respect of important functional outcomes. Sadly, preterm feeding remains characterised by a deficit of evidence. In this chapter, we will briefly describe the history of preterm nutrition, discuss current enteral and parenteral practice, important evidence gaps, a summary of approaches for evaluating nutritional practice, and key considerations for future endeavour. Our discussion refers to all extremely preterm infants and it not confined to the micro preemie.

Use of parenteral nutrition in the first postnatal week in England and Wales: an observational study using real-world data.

BACKGROUND: Parenteral nutrition (PN) is used to provide supplemental support to neonates while enteral feeding is being established. PN is a high-cost intervention with beneficial and harmful effects. Internationally, there is substantial variation in how PN is used, and there are limited contemporary data describing use across Great Britain. OBJECTIVE: To describe PN use in the first postnatal week in infants born and admitted to neonatal care in England, Scotland and Wales. METHOD: Data describing neonates admitted to National Health Service neonatal units between 1 January 2012 and 31 December 2017, extracted from routinely recorded data held the National Neonatal Research Database (NNRD); the denominator was live births, from Office for National Statistics. RESULTS: Over the study period 62 145 neonates were given PN in the first postnatal week (1.4% of all live births); use was higher in more preterm neonates (76% of livebirths at <28 weeks, 0.2% of term livebirths) and in neonates with lower birth weight. 15% (9181/62145) of neonates given PN in the first postnatal week were born at term. There was geographic variation in PN administration: the proportion of live births given PN within neonatal regional networks ranged from 1.0% (95% CIs 1.0 to 1.0) to 2.8% (95% CI 2.7 to 2.9). CONCLUSIONS AND RELEVANCE: Significant variation exists in neonatal PN use; it is unlikely this reflects optimal use of an expensive intervention. Research is needed to identify which babies will benefit most and which are at risk of harm from early PN. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT03767634; registration date: 6 December 2018.

Outcomes in relation to early parenteral nutrition use in preterm neonates born between 30 and 33 weeks' gestation: a propensity score matched observational study.

OBJECTIVE: To evaluate whether in preterm neonates parenteral nutrition use in the first 7 postnatal days, compared with no parenteral nutrition use, is associated with differences in survival and other important morbidities. Randomised trials in critically ill older children show that harms, such as nosocomial infection, outweigh benefits of early parenteral nutrition administration; there is a paucity of similar data in neonates. DESIGN: Retrospective cohort study using propensity matching including 35 maternal, infant and organisational factors to minimise bias and confounding. SETTING: National, population-level clinical data obtained for all National Health Service neonatal units in England and Wales. PATIENTS: Preterm neonates born between 30+0 and 32+6 weeks+days. INTERVENTIONS: The exposure was parenteral nutrition administered in the first 7 days of postnatal life; the comparator was no parenteral nutrition. MAIN OUTCOME MEASURES: The primary outcome was survival to discharge from neonatal care. Secondary outcomes comprised the neonatal core outcome set. RESULTS: 16 292 neonates were compared in propensity score matched analyses. Compared with matched neonates not given parenteral nutrition in the first postnatal week, neonates who received parenteral nutrition had higher survival at discharge (absolute rate increase 0.91%; 95% CI 0.53% to 1.30%), but higher rates of necrotising enterocolitis (absolute rate increase 4.6%), bronchopulmonary dysplasia (absolute rate increase 3.9%), late-onset sepsis (absolute rate increase 1.5%) and need for surgical procedures (absolute rate increase 0.92%). CONCLUSIONS: In neonates born between 30+0 and 32+6 weeks' gestation, those given parenteral nutrition in the first postnatal week had a higher rate of survival but higher rates of important neonatal morbidities. Clinician equipoise in this area should be resolved by prospective randomised trials. TRIAL REGISTRATION NUMBER: NCT03767634.

National priority setting partnership using a Delphi consensus process to develop neonatal research questions suitable for practice-changing randomised trials in the United Kingdom.

INTRODUCTION: Methodologically robust clinical trials are required to improve neonatal care and reduce unwanted variations in practice. Previous neonatal research prioritisation processes have identified important research themes rather than specific research questions amenable to clinical trials. Practice-changing trials require well-defined research questions, commonly organised using the Population, Intervention, Comparison, Outcome (PICO) structure. By narrowing the scope of research priorities to those which can be answered in clinical trials and by involving a wide range of different stakeholders, we aim to provide a robust and transparent process to identify and prioritise research questions answerable within the National Healthcare System to inform future practice-changing clinical trials. METHODS AND ANALYSIS: A steering group comprising parents, doctors, nurses, allied health professionals, researchers and representatives from key organisations (Neonatal Society, British Association of Perinatal Medicine, Neonatal Nurses Association and Royal College of Paediatrics and Child Health) was identified to oversee this project. We will invite submissions of research questions formatted using the PICO structure from the following stakeholder groups using an online questionnaire: parents, patients, healthcare professionals and academic researchers. Unanswered, non-duplicate research questions will be entered into a three-round eDelphi survey of all stakeholder groups. Research questions will be ranked by mean aggregate scores. ETHICS AND DISSEMINATION: The final list of prioritised research questions will be disseminated through traditional academic channels, directly to key stakeholder groups through representative organisations and on social media. The outcome of the project will be shared with key research organisations such as the National Institute for Health Research. Research ethics committee approval is not required.

Standardized Outcome Measures for Preterm and Hospitalized Neonates: An ICHOM Standard Set.

INTRODUCTION: Approximately, one in ten infants is born preterm or requires hospitalization at birth. These complications at birth have long-term consequences that can extend into childhood and adulthood. Timely detection of developmental delay through surveillance could enable tailored support for these babies and their families. However, the possibilities for follow-up are limited, especially in middle- and low-income countries, and the tools to do so are either not available or too expensive. A standardized and core set of outcomes for neonates, with feasible tools for evaluation and follow-up, could result in improving quality, enhance shared decision-making, and enable global benchmarking. METHODS: The International Consortium for Health Outcomes Measurement (ICHOM) convened an international working group, which was comprised of 14 health-care professionals (HCP) and 6 patient representatives in the field of neonatal care. An outcome set was developed using a three-round modified Delphi process, and it was endorsed through a patient representative-validation survey and an HCP survey. RESULTS: A literature review revealed 1,076 articles and 26 registries which were screened for meaningful outcomes, patient-reported outcome measures, clinical measures, and case mix variables. This resulted in a neonatal set with 21 core outcomes covering three domains (physical, social, and mental functioning) and 14 tools to assess these outcomes at three timepoints. DISCUSSION: This set can be implemented globally and it will allow comparison of outcomes across different settings and countries. The transparent consensus-driven development process which involved stakeholders and professionals from all over the world ensures global relevance.

Adding value to core outcome set development using multimethod systematic reviews.

Trials evaluating the same interventions rarely measure or report identical outcomes. This limits the possibility of aggregating effect sizes across studies to generate high-quality evidence through systematic reviews and meta-analyses. To address this problem, core outcome sets (COS) establish agreed sets of outcomes to be used in all future trials. When developing COS, potential outcome domains are identified by systematically reviewing the outcomes of trials, and increasingly, through primary qualitative research exploring the experiences of key stakeholders, with relevant outcome domains subsequently determined through transdisciplinary consensus development. However, the primary qualitative component can be time consuming with unclear impact. We aimed to examine the potential added value of a qualitative systematic review alongside a quantitative systematic review of trial outcomes to inform COS development in neonatal care using case analysis methods. We compared the methods and findings of a scoping review of neonatal trial outcomes and a scoping review of qualitative research on parents', patients', and professional caregivers' perspectives of neonatal care. Together, these identified a wider range and greater depth of health and social outcome domains, some unique to each review, which were incorporated into the subsequent Delphi process and informed the final set of core outcome domains. Qualitative scoping reviews of participant perspectives research, used in conjunction with quantitative scoping reviews of trials, could identify more outcome domains for consideration and could provide greater depth of understanding to inform stakeholder group discussion in COS development. This is an innovation in the application of research synthesis methods.

Interventions to improve quantitative measures of parent satisfaction in neonatal care: a systematic review.

OBJECTIVE: Interventions improving parent satisfaction can reduce parent stress, may improve parent-infant bonding and infant outcomes. Our objective was to systematically review neonatal interventions relating to parents of infants of all gestations where an outcome was parent satisfaction. METHODS: We searched the databases MEDLINE, EMBASE, PsychINFO, Cochrane Central Register of Controlled Trials, CINAHL, HMIC, Maternity and Infant Care between 1 January 1946 and 1 October 2017. Inclusion criteria were randomised controlled trials (RCT), cohort studies and other non-randomised studies if participants were parents of infants receiving neonatal care, interventions were implemented in neonatal units (of any care level) and ≥1 quantitative outcome of parent satisfaction was measured. Included studies were limited to the English language only. We extracted study characteristics, interventions, outcomes and parent involvement in intervention design. Included studies were not sufficiently homogenous to enable quantitative synthesis. We assessed quality with the Cochrane Collaboration risk of bias tool (randomised) and the ROBINS-I tool (Risk Of Bias In Non-randomised Studies - of Interventions) (non-randomised studies). RESULTS: We identified 32 studies with satisfaction measures from over 2800 parents and grouped interventions into 5 themes. Most studies were non-randomised involving preterm infants. Parent satisfaction was measured by 334 different questions in 29 questionnaires (only 6/29 fully validated). 18/32 studies reported higher parent satisfaction in the intervention group. The intervention theme with most studies reporting higher satisfaction was parent involvement (10/14). Five (5/32) studies reported involving parents in intervention design. All studies had high risk of bias. CONCLUSIONS: Many interventions, commonly relating to parent involvement, are reported to improve parent satisfaction. Inconsistency in satisfaction measurements and high risk of bias makes this low-quality evidence. Standardised, validated parent satisfaction measures are needed, as well as higher quality trials of parent experience involving parents in intervention design. PROSPERO REGISTRATION NUMBER: CRD42017072388.

Inconsistent outcome reporting in large neonatal trials: a systematic review.

OBJECTIVE: Inconsistent outcome selection and reporting in clinical trials are important sources of research waste; it is not known how common this problem is in neonatal trials. Our objective was to determine whether large clinical trials involving infants receiving neonatal care report a consistent set of outcomes, how composite outcomes are used and whether parents or former patients were involved in outcome selection. DESIGN: A literature search of CENTRAL, CINAHL, EMBASE and MEDLINE was conducted; randomised trials published between 1 July 2012 and 1 July 2017 and involving at least 100 infants in each arm were included. Outcomes and outcome measures were extracted and categorised by physiological system; reported former patient and parent involvement in outcome selection was extracted. RESULTS: Seventy-six trials involving 43 126 infants were identified; 216 different outcomes with 889 different outcome measures were reported. Outcome reporting covered all physiological systems but was variable between individual trials: only 67/76 (88%) of trials reported survival and 639 outcome measures were only reported in a single trial. Thirty-three composite outcomes were used in 41 trials. No trials reported former patient or parent involvement in outcome selection. CONCLUSIONS: Inconsistent outcome reporting and a lack of parent and former patient involvement in outcome selection in neonatal clinical trials limits the ability of such trials to answer clinically meaningful questions. Developing and implementing a core outcome set for future neonatal trials, with input from all stakeholders, should address these issues.

Late Administration of Surfactant May Increase the Risk of Patent Ductus Arteriosus.

Introduction: Early rescue surfactant is the most effective way of administering surfactant but many infants still receive surfactant later. Our aim was to explore the association between timing of surfactant administration and the development of patent ductus arteriosus and other neonatal morbidities. Materials and method: This retrospective study analyzed 819 preterm infants under 30 weeks of gestational age and under 1,500 g. Results: Five hundred and ninety three infants received surfactant during the study period, of these 365 received it within 2 h of life (early group) and 228 received it after two h (late group). Patent ductus arteriosus was detected in 175 (48%) of the early group and 168 (74%) of the late group, p = 0.001. Multinominal logistic regression analysis demonstrated that receiving surfactant after 2 h of life has a OR 3.5 (2.2-5.64 95 % CI) and a p-value of 0.001 for developing patent ductus arteriosus. Conclusion: In this study population we observed that late surfactant administration is associated with increased risk of patent ductus arteriosus.