Inter-Specialty Differences in the Management of Febrile Neonates on Prostaglandin E1

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Study Design A cross-sectional, web-based survey was distributed to 800 neonatologists and pediatric cardiac intensivists in North America, Europe, and the Middle East. Respondents (n=526) were queried regarding their management of a clinical vignette involving a febrile neonate on PGE1, including decisions about sepsis work-up, antibiotic administration, and lumbar puncture. Data were analyzed using chi-square tests and multivariate logistic regression. Result Pediatric cardiac intensivists were significantly more likely to initiate full sepsis work-up and antibiotic therapy (65.6% vs. 38.7%, p<0.001). Specialty was the only significant predictor of antibiotic administration (OR=3.07, 95% CI: 1.76–4.40, p<0.001). No significant differences were found in lumbar puncture practices. Conclusion Significant inter-specialty variation exists in the management of febrile neonates on PGE1, highlighting the need for evidence-based guidelines to standardize care and optimize antimicrobial stewardship. Health sciences/Risk factors Health sciences/Medical research/Outcomes research Alprostadil Fever Infant Newborn Heart Defects Congenital Practice Patterns Physicians' Anti-Bacterial Agents Introduction Prostaglandin E1 (PGE1, alprostadil) is a cornerstone therapy in the neonatal management of duct-dependent congenital heart disease (CHD), enabling the maintenance of ductal patency and thereby supporting either systemic or pulmonary circulation until definitive surgical or catheter-based intervention is feasible. [ 1 ] In conditions such as pulmonary atresia, critical coarctation of the aorta, or hypoplastic left heart syndrome, the patency of the ductus arteriosus is essential for adequate systemic or pulmonary perfusion. [ 2 ] The use of PGE1 in this context has transformed survival outcomes for these neonates. However, while lifesaving, PGE1 is frequently associated with adverse effects, particularly fever, which occurs in up to 40% of treated neonates. [ 3 , 4 ] Fever in neonates less than 28 days of age remains a clinical red flag, strongly associated with serious bacterial infections including bacteremia, meningitis, and urinary tract infections. [ 5 ] Current pediatric and neonatal guidelines advise a full sepsis evaluation, including blood cultures, lumbar puncture (LP), and prompt empiric administration of intravenous antibiotics when fever is present. [ 6 – 8 ] However, in neonates receiving PGE1, the etiology of fever becomes diagnostically challenging. Fever may reflect a benign pharmacologic effect of the medication, an effect previously well-documented, [ 3 , 4 ] or it may represent a true infectious process. This ambiguity poses a complex dilemma: under-treatment risks missing a life-threatening infection, whereas over-treatment may lead to unnecessary invasive procedures, prolonged hospitalization, disruption of cardiac care plans, and contribution to antimicrobial resistance. [ 9 – 11 ] The lack of dedicated evidence or standardized clinical guidelines addressing fever management in neonates treated with PGE1 has led to wide practice variation. Some clinicians may favor a conservative approach, attributing the fever to PGE1 and observing without intervention, while others proceed with a full infectious evaluation and antibiotic therapy to err on the side of caution. [ 4 , 10 ] In real-world practice, this results in a spectrum of responses ranging from no evaluation at all to full sepsis work-up including LP and broad-spectrum antibiotics. Such variability may be influenced by provider specialty, training, institutional protocols, and regional medical culture. Differences between neonatologists and pediatric cardiac intensivists may be particularly relevant. For instance, a study by Borenstein-Levin et al. found significant inter-specialty differences in approaches to ventilation, sedation, hemodynamics, and vascular access in the care of the same critically ill neonates. [ 12 ] Given the clinical consequences of both under- and over-treatment of febrile neonates, it is important to better understand these practice patterns. This study seeks to evaluate and compare the clinical approaches of neonatologists and pediatric cardiac intensivists regarding the management of fever in neonates receiving PGE1 for duct-dependent CHD. By identifying patterns and predictors of practice variation, this research aims to inform future guidelines, promote more standardized care, and support balanced antimicrobial stewardship in this vulnerable patient population. Methods Study Design and Objectives We conducted a cross-sectional, web-based survey to evaluate inter-specialty differences in the management of febrile neonates receiving PGE1 for ductal patency. The study aimed to compare the diagnostic and therapeutic strategies of neonatologists and pediatric cardiac intensivists regarding sepsis evaluation, antibiotic administration, and LP performance. Additional objectives included exploring whether additional provider characteristics (e.g., specialty, region of practice, years of experience, and sex) predict management decisions in this clinical context. Survey Development The survey instrument was developed by a multidisciplinary team of neonatologists and pediatric cardiac intensivists, based on expert consensus and a review of existing literature on neonatal fever management and PGE1 therapy. The survey included both multiple-choice and scaled-response questions organized into the following sections: - Demographics and professional background - Clinical practice setting and experience - Management approaches to a clinical vignette describing a febrile neonate receiving PGE1 - Decision-making regarding sepsis work-up, antibiotic initiation, and lumbar puncture Survey items were pretested for clarity and content validity by a small group of specialists (n = 8) not included in the final sample. Modifications were made accordingly. Participants and Distribution The target population included board-certified neonatologists and pediatric cardiac intensivists practicing in North America, Europe, and the Middle East. A convenience sample of 800 physicians was invited to participate via professional mailing lists and institutional collaborations. Survey participation was anonymous and voluntary. No personal identifiers were collected to preserve confidentiality. Data Collection and Variables The survey was administered online using a secure, GDPR-compliant platform. Respondents were asked to indicate: - Their primary specialty (neonatology or pediatric cardiac intensive care) - Country and region of practice - Years of clinical experience - Sex - Approach to fever in a neonate receiving PGE1, including: - Whether a sepsis work-up would be initiated - Whether antibiotic therapy would be started - Whether a LP would be performed, and under what clinical criteria Management options were offered as categorical variables (e.g., full work-up with antibiotics, partial work-up without antibiotics, etc.). Responses were coded and entered as a de-identified dataset for analysis. Statistical Analysis Descriptive statistics were used to summarize demographic data and response distributions. Categorical variables were presented as counts and percentages. Differences in management strategies between specialties were assessed using Chi-square tests. The threshold for statistical significance was set at p < 0.05. Multivariate logistic regression models were constructed to identify independent predictors of: Antibiotic administration, Performance of a full sepsis work-up, Decision to perform a LP. Covariates in the models included specialty, sex, region of practice, and years of clinical experience. Odds ratios (ORs) and 95% confidence intervals (CIs) were reported. All analyses were performed using Python (v3.10) with appropriate statistical libraries (pandas, scipy.stats, and statsmodels). Ethical Considerations This study involved no patient-level data and did not require ethical approval under institutional guidelines for anonymous survey-based research. Participation implied consent, and respondents were informed of the anonymous nature of data handling and publication. Results Survey Participation and Respondent Characteristics Of the 800 physicians invited to participate, 526 completed the survey, yielding a response rate of 65.8%. The respondents included 282 neonatologists (53.6%) and 244 pediatric cardiac intensivists (46.4%). Participants were geographically distributed across North America (58.6%), Europe (26.6%), and the Middle East (14.8%). Regarding clinical experience, 25.3% reported 20 years of experience. Slightly more than half of the respondents were female (53.2%). A summary of the demographic characteristics is presented in Table 1 . Table 1 Demographic Characteristics of Survey Respondents ( N = 526) Characteristic Category n % Specialty Neonatologist 282 53.6 Pediatric Cardiac Intensivist 244 46.4 Geographic Region North America 308 58.6 Europe 140 26.6 Middle East 78 14.8 Years of Experience 20 years 80 15.2 Sex Male 246 46.8 Female 280 53.2 Fever Management and Lumbar Puncture Practices Fever management approaches for neonates receiving PGE1 varied significantly by specialty. Pediatric cardiac intensivists were more likely to initiate a full sepsis work-up including antibiotics compared to neonatologists (65.6% vs. 38.7%, χ² = 38.32, p < 0.001). Neonatologists more frequently opted for no work-up or partial work-up without antibiotics. Fever management strategies were not significantly influenced by region (χ² = 17.79, p = 0.120), sex (χ² = 4.78, p = 0.310), or years of experience (χ² = 29.79, p = 0.106). Lumbar puncture decision-making was not significantly different between the specialties (χ² = 5.70, p = 0.223). However, pediatric cardiac intensivists were more likely to perform LP based on laboratory findings or routine protocols, while neonatologists more often cited systemic signs or clinical deterioration. Differences in LP triggers were not statistically significant across region (χ² = 20.79, p = 0.139), sex (χ² = 6.83, p = 0.234), or experience (χ² = 23.40, p = 0.183). A detailed comparison of fever management and LP practices by specialty is presented in Table 2 . Table 2 Fever Management Practices by Medical Specialty 1. Management Strategy Neonatologists (n = 282) Cardiac Intensivists (n = 244) p-value Sepsis Evaluation Approach Full sepsis work-up + empiric antibiotics 109 (38.7%) 160 (65.6%) < 0.001* Full sepsis work-up, no antibiotics 45 (16.0%) 35 (14.3%) 0.660 Partial work-up, no antibiotics 79 (28.0%) 76 (31.0%) 0.002* No work-up 65 (23.0%) 89 (36.5%) < 0.001* Lumbar Puncture Indications Clinical deterioration 46 (16.3%) 37 (15.2%) 0.723 Abnormal laboratory results 49 (17.4%) 56 (23.0%) 0.135 Systemic signs of infection 53 (18.8%) 49 (20.1%) 0.709 Routine practice 56 (19.9%) 56 (23.0%) 0.412 Other indications 78 (27.7%) 46 (18.9%) 0.010* *Statistically significant (p < 0.05) Predictors of Antibiotic Use and Full Work-up Antibiotic Administration. Multivariate logistic regression identified specialty as a significant predictor of antibiotic administration. Pediatric cardiac intensivists had 3.07 times higher odds of initiating antibiotics for a febrile neonate receiving PGE1 compared to neonatologists (OR = 3.07; 95% CI, 1.76–4.40; p < 0.001). Sex, region, and clinical experience were not statistically significant predictors (Table 3 ). Table 3 Multivariable Predictors of Empiric Antibiotic Administration Predictor Variable Odds Ratio 95% Confidence Interval p-value Specialty Cardiac Intensivist vs. Neonatologist 3.07 1.76–4.40 10 years vs. <5 years 0.94 0.60–1.49 0.806 *Statistically significant (p < 0.05) Full Sepsis Work-up. Similar results were found for the likelihood of performing a full sepsis work-up, with pediatric cardiac intensivists and clinicians from North America demonstrating significantly increased odds (OR = 2.92; 95% CI, 1.74–4.21; p < 0.001). Other variables were not significant. Lumbar Puncture. No variables, including specialty, sex, region, or experience, were independently associated with LP performance in the multivariate analysis. Discussion This cross-sectional survey reveals significant inter-specialty differences in the management of febrile neonates receiving PGE1 therapy. Our findings demonstrate that pediatric cardiac intensivists are substantially more likely than neonatologists to initiate full sepsis workups with empiric antibiotic therapy, with more than three-fold increased odds of antibiotic administration. These results highlight a critical gap in standardized care for this vulnerable population and underscore the need for evidence-based guidelines to optimize clinical decision-making. Clinical Implications and Patient Safety Considerations The substantial practice variation identified in our study raises important questions about optimal care for febrile neonates receiving PGE1. Both over-treatment and under-treatment may carry significant risks. Aggressive sepsis evaluation and empiric antibiotic therapy may lead to unnecessary invasive procedures, prolonged hospitalization, increased healthcare costs, and contribution to antimicrobial resistance. [ 13 , 14 ] LP in neonates with complex congenital heart disease may pose additional procedural risks, particularly in those with ductal-dependent circulation where hemodynamic instability could be precipitated by positioning or procedural stress. [ 15 ] Conversely, conservative management risks missing life-threatening bacterial infections. Early-onset sepsis remains a leading cause of neonatal morbidity and mortality, with case fatality rates of 10–15% for bacteremia and up to 25% for meningitis. [ 5 , 16 ] The immunocompromised state of critically ill neonates with congenital heart disease may further increase susceptibility to serious bacterial infections. [ 17 ] The absence of statistically significant differences in LP practices between specialties, despite differences in overall sepsis work-up approaches, suggests that both groups recognize the procedural risks and complexity of LP in this population. However, the variation in clinical triggers for LP (laboratory findings versus clinical deterioration) indicates ongoing uncertainty about optimal indications. Factors Influencing Practice Patterns Our analysis revealed that demographic factors such as clinician sex, years of experience, and geographic region were not significant predictors of management decisions. This suggests that specialty-specific training and culture, rather than individual clinician characteristics, are the primary drivers of practice variation. The lack of regional differences is somewhat surprising given documented variations in antibiotic prescribing patterns and sepsis management protocols across different healthcare systems. [ 18 , 19 ] The absence of experience-related differences indicates that practice patterns are established early in specialty training and remain consistent throughout career progression. This finding supports the importance of evidence-based education and standardized protocols during residency and fellowship training programs. Toward Evidence-Based Guidelines The substantial practice variation documented in our study underscores the urgent need for evidence-based guidelines specific to fever management in neonates receiving PGE1. Current pediatric sepsis guidelines do not address the unique clinical context of drug-induced fever in critically ill neonates with congenital heart disease. [ 20 , 21 ] Several strategies could help optimize care for this population. First, development of clinical prediction rules incorporating patient-specific factors (hemodynamic stability, biomarkers, duration of PGE1 therapy, etc.) could guide risk stratification and management decisions. [ 22 ] Second, implementation of standardized protocols that balance infection risk with the potential harms of over-treatment could reduce practice variation while maintaining safety. [ 23 ] Third, prospective studies examining outcomes associated with different management approaches could provide evidence to inform future guidelines. Recent studies have begun to address this knowledge gap in managing fever in neonates receiving PGE1. Baranwal et al. conducted a prospective study demonstrating that presepsin may help differentiate between PGE1-induced systemic inflammation and true bacterial sepsis, offering a potential biomarker to reduce unnecessary antibiotic administration in this unique population. [ 24 ] Similarly, C-reactive protein and procalcitonin have shown utility in early-onset neonatal sepsis and may aid in distinguishing infectious from non-infectious causes of fever. [ 25 , 26 ] These biomarkers, when interpreted in the context of PGE1 therapy, could contribute to more nuanced decision-making and support a selective approach to antimicrobial use. Future Research Directions Our findings highlight several areas for future investigation. Prospective cohort studies examining clinical outcomes associated with different management strategies would provide critical evidence for guideline development. Additionally, research into biomarkers that can reliably distinguish PGE1-induced fever from infectious fever could revolutionize clinical decision-making in this population. Cost-effectiveness analyses comparing aggressive versus conservative management approaches could inform resource allocation and policy decisions. Finally, implementation studies evaluating the effectiveness of standardized protocols in reducing practice variation while maintaining patient safety would be valuable for healthcare systems seeking to optimize care quality. Limitations Several limitations should be considered when interpreting our findings. First, the cross-sectional survey design captures reported practice patterns rather than actual clinical outcomes, limiting our ability to determine which approach leads to better patient outcomes. The clinical vignette methodology, while standardized, may not fully capture the complexity of real-world decision-making where multiple clinical factors influence management choices. Second, selection bias may have influenced our results, as physicians who chose to participate in the survey may differ systematically from non-respondents in their practice patterns or interest in evidence-based medicine. The 65.8% response rate, while reasonable for physician surveys, leaves open the possibility that non-respondents have different practice patterns. Third, our convenience sampling approach may not fully represent the broader population of neonatologists and pediatric cardiac intensivists. The geographic distribution of respondents, while spanning three continents, may not reflect global practice patterns, particularly in resource-limited settings where diagnostic capabilities and antibiotic availability may influence management decisions. Fourth, the survey instrument, despite pretesting and expert review, may not have captured all relevant clinical factors that influence decision-making in practice. Social desirability bias may have led some respondents to report practices that align with perceived best practices rather than their actual clinical behavior. Finally, our study did not collect data on institutional protocols or local guidelines that may influence individual clinician decision-making. Practice variation may be partially explained by differences in institutional culture and protocols rather than individual clinician preferences alone. Conclusions This multinational survey demonstrates significant inter-specialty differences in the management of febrile neonates receiving PGE1 therapy, with pediatric cardiac intensivists substantially more likely to pursue aggressive sepsis evaluation and empiric antibiotic therapy compared to neonatologists. These findings highlight the absence of evidence-based guidelines for this clinical scenario and underscore the need for standardized approaches that balance infection risk with the potential harms of over-treatment. The substantial practice variation identified in our study represents a serious gap in pediatric healthcare that requires appropriate attention. Development of evidence-based clinical guidelines, informed by prospective outcome studies and validated risk stratification tools, is essential to optimize care for this vulnerable population. Such guidelines should incorporate specialty-specific perspectives while prioritizing patient safety and antimicrobial stewardship principles. Future research should focus on prospective studies examining clinical outcomes associated with different management strategies, development of biomarkers to distinguish infectious from drug-induced fever, and implementation of standardized protocols that can reduce practice variation while maintaining high-quality care. Only through such collaborative efforts can we ensure that neonates with life-threatening congenital heart disease receive optimal, evidence-based care during their most vulnerable period. Abbreviations PGE1 Prostaglandin E1 CHD Congenital heart disease LP Lumbar puncture Declarations Acknowledgement: None Statement of Ethics This study involved no patient-level data and the institutional research board (IRB) exempted ethical approval under institutional guidelines for anonymous survey-based research. Participation implied consent, and respondents were informed of the anonymous nature of data handling and publication. Conflict of Interest Disclosures (includes financial disclosures): All authors have no conflicts of interest to declare. Funding/Support: This study was not supported by any sponsor or funder. Author Contribution Dr. Sharon Morag conceptualized and designed the study, drafted the initial manuscript, and critically reviewed and revised the manuscript. Drs. Alexander Lowenthal and Hiba Abuelhija designed the survey, designed the data collection instruments, collected data, carried out the initial analyses, and critically reviewed and revised the manuscript. Dr. Uri Pollak conceptualized and designed the study, coordinated and supervised data collection, and critically reviewed and revised the manuscript for important intellectual content. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work. Data Availability Statement The de-identified dataset supporting the conclusions of this article is available from the corresponding author (Dr. Uri Pollak, [email protected] ) upon reasonable request for legitimate research purposes. Requests must include a detailed research proposal, institutional affiliation verification, and appropriate ethical approval where required. Data will be shared in standard formats with documentation, subject to conditions ensuring participant confidentiality, data security, and appropriate attribution of the original study. References Freed MD, Heymann MA, Lewis AB, Roehl SL, Kensey RC. Prostaglandin E1 infants with ductus arteriosus-dependent congenital heart disease. Circulation . 1981;64(5):899–905. doi: 10.1161/01.cir.64.5.899 Heymann MA, Clyman RI. Evaluation of alprostadil (prostaglandin E1) in the management of congenital heart disease in infancy. 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Cite Share Download PDF Status: Published Journal Publication published 24 Nov, 2025 Read the published version in Journal of Perinatology → Version 1 posted Editorial decision: revise 10 Sep, 2025 Review # 1 received at journal 01 Sep, 2025 Reviewer # 3 agreed at journal 01 Sep, 2025 Review # 2 received at journal 01 Aug, 2025 Reviewer # 2 agreed at journal 19 Jul, 2025 Reviewer # 1 agreed at journal 17 Jul, 2025 Reviewers invited by journal 17 Jul, 2025 Submission checks completed at journal 02 Jul, 2025 Editor assigned by journal 01 Jul, 2025 First submitted to journal 01 Jul, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7023048","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":486889987,"identity":"2d3ca608-5d77-4a88-a671-7b3db7ff95e0","order_by":0,"name":"Uri Pollak","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA6klEQVRIiWNgGAWjYFACxgYGhgKbBAaGBBDvAEQwoYCQFoM0dC0GhGwyOIymhQGPFoPbh9sefDA4n8ffnvz444+aOwz80scvMDzAp+VcYrvhDIPbxRJnnplJ8xx7xiDZl1OA12EGZxjbpHkMbic23EgwY2ZgOwwU4UkgRsu5xPk30j9//PGPeC0HEjfcyDGQ4G0DaWE/gFeL5BlGkF+SEzeeeVMmzdt3mEeyh4fhAD4tfGfYnz34UGGXOO94+uaPP74dluPnYX/48EcFbi1AwIbC4wEigwN4NaBrAQL2BwR0jIJRMApGwQgDAJ5+VskqmqP+AAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0002-4575-3888","institution":"Hadassah University Medical Center","correspondingAuthor":true,"prefix":"","firstName":"Uri","middleName":"","lastName":"Pollak","suffix":""},{"id":486889988,"identity":"fb01cc36-f91e-4e3d-9622-68242ebd2e9c","order_by":1,"name":"Sharon Morag","email":"","orcid":"","institution":"Dana Dwek Children's Hospital, Tel Aviv Sourasky Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Sharon","middleName":"","lastName":"Morag","suffix":""},{"id":486889989,"identity":"46521c3e-cf92-49fe-bc70-06cd2a4596b0","order_by":2,"name":"Alexander Lowenthal","email":"","orcid":"","institution":"Dana Dwek Children's Hospital, Tel Aviv Sourasky Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Alexander","middleName":"","lastName":"Lowenthal","suffix":""},{"id":486889990,"identity":"ae2efe47-5ba4-4b8d-9bf7-bb966c5f4f60","order_by":3,"name":"Hiba Abuelhija","email":"","orcid":"","institution":"Hadassah University Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Hiba","middleName":"","lastName":"Abuelhija","suffix":""}],"badges":[],"createdAt":"2025-07-01 19:05:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7023048/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7023048/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41372-025-02512-w","type":"published","date":"2025-11-24T05:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":96699331,"identity":"60f6d6e4-a01b-4c4e-ab0f-5c239684afe6","added_by":"auto","created_at":"2025-11-25 08:10:04","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":874450,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7023048/v1/6c3b1a18-67c3-4572-97a6-310bfdaba2cc.pdf"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e conflict of interest to disclose.","formattedTitle":"Inter-Specialty Differences in the Management of Febrile Neonates on Prostaglandin E1","fulltext":[{"header":"Introduction","content":"\u003cp\u003eProstaglandin E1 (PGE1, alprostadil) is a cornerstone therapy in the neonatal management of duct-dependent congenital heart disease (CHD), enabling the maintenance of ductal patency and thereby supporting either systemic or pulmonary circulation until definitive surgical or catheter-based intervention is feasible. [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] In conditions such as pulmonary atresia, critical coarctation of the aorta, or hypoplastic left heart syndrome, the patency of the ductus arteriosus is essential for adequate systemic or pulmonary perfusion. [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] The use of PGE1 in this context has transformed survival outcomes for these neonates. However, while lifesaving, PGE1 is frequently associated with adverse effects, particularly fever, which occurs in up to 40% of treated neonates. [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eFever in neonates less than 28 days of age remains a clinical red flag, strongly associated with serious bacterial infections including bacteremia, meningitis, and urinary tract infections. [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] Current pediatric and neonatal guidelines advise a full sepsis evaluation, including blood cultures, lumbar puncture (LP), and prompt empiric administration of intravenous antibiotics when fever is present. [\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] However, in neonates receiving PGE1, the etiology of fever becomes diagnostically challenging. Fever may reflect a benign pharmacologic effect of the medication, an effect previously well-documented, [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] or it may represent a true infectious process. This ambiguity poses a complex dilemma: under-treatment risks missing a life-threatening infection, whereas over-treatment may lead to unnecessary invasive procedures, prolonged hospitalization, disruption of cardiac care plans, and contribution to antimicrobial resistance. [\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/p\u003e \u003cp\u003e The lack of dedicated evidence or standardized clinical guidelines addressing fever management in neonates treated with PGE1 has led to wide practice variation. Some clinicians may favor a conservative approach, attributing the fever to PGE1 and observing without intervention, while others proceed with a full infectious evaluation and antibiotic therapy to err on the side of caution. [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] In real-world practice, this results in a spectrum of responses ranging from no evaluation at all to full sepsis work-up including LP and broad-spectrum antibiotics. Such variability may be influenced by provider specialty, training, institutional protocols, and regional medical culture.\u003c/p\u003e \u003cp\u003eDifferences between neonatologists and pediatric cardiac intensivists may be particularly relevant. For instance, a study by Borenstein-Levin et al. found significant inter-specialty differences in approaches to ventilation, sedation, hemodynamics, and vascular access in the care of the same critically ill neonates. [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eGiven the clinical consequences of both under- and over-treatment of febrile neonates, it is important to better understand these practice patterns. This study seeks to evaluate and compare the clinical approaches of neonatologists and pediatric cardiac intensivists regarding the management of fever in neonates receiving PGE1 for duct-dependent CHD. By identifying patterns and predictors of practice variation, this research aims to inform future guidelines, promote more standardized care, and support balanced antimicrobial stewardship in this vulnerable patient population.\u003c/p\u003e "},{"header":"Methods","content":" \u003cp\u003e \u003cb\u003eStudy Design and Objectives\u003c/b\u003e \u003c/p\u003e \u003cp\u003eWe conducted a cross-sectional, web-based survey to evaluate inter-specialty differences in the management of febrile neonates receiving PGE1 for ductal patency. The study aimed to compare the diagnostic and therapeutic strategies of neonatologists and pediatric cardiac intensivists regarding sepsis evaluation, antibiotic administration, and LP performance. Additional objectives included exploring whether additional provider characteristics (e.g., specialty, region of practice, years of experience, and sex) predict management decisions in this clinical context.\u003c/p\u003e \u003cp\u003e \u003cb\u003eSurvey Development\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThe survey instrument was developed by a multidisciplinary team of neonatologists and pediatric cardiac intensivists, based on expert consensus and a review of existing literature on neonatal fever management and PGE1 therapy. The survey included both multiple-choice and scaled-response questions organized into the following sections:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e- Demographics and professional background\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e- Clinical practice setting and experience\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e- Management approaches to a clinical vignette describing a febrile neonate receiving PGE1\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e- Decision-making regarding sepsis work-up, antibiotic initiation, and lumbar puncture\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eSurvey items were pretested for clarity and content validity by a small group of specialists (n\u0026thinsp;=\u0026thinsp;8) not included in the final sample. Modifications were made accordingly.\u003c/p\u003e \u003cp\u003e \u003cb\u003eParticipants and Distribution\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThe target population included board-certified neonatologists and pediatric cardiac intensivists practicing in North America, Europe, and the Middle East. A convenience sample of 800 physicians was invited to participate via professional mailing lists and institutional collaborations. Survey participation was anonymous and voluntary. No personal identifiers were collected to preserve confidentiality.\u003c/p\u003e \u003cp\u003e \u003cb\u003eData Collection and Variables\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThe survey was administered online using a secure, GDPR-compliant platform. Respondents were asked to indicate:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e- Their primary specialty (neonatology or pediatric cardiac intensive care)\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e- Country and region of practice\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e- Years of clinical experience\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e- Sex\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e- Approach to fever in a neonate receiving PGE1, including:\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e- Whether a sepsis work-up would be initiated\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e- Whether antibiotic therapy would be started\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e- Whether a LP would be performed, and under what clinical criteria\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eManagement options were offered as categorical variables (e.g., full work-up with antibiotics, partial work-up without antibiotics, etc.). Responses were coded and entered as a de-identified dataset for analysis.\u003c/p\u003e \u003cdiv id=\"Sec2\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eDescriptive statistics were used to summarize demographic data and response distributions. Categorical variables were presented as counts and percentages. Differences in management strategies between specialties were assessed using Chi-square tests. The threshold for statistical significance was set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003cp\u003eMultivariate logistic regression models were constructed to identify independent predictors of: Antibiotic administration, Performance of a full sepsis work-up, Decision to perform a LP.\u003c/p\u003e \u003cp\u003eCovariates in the models included specialty, sex, region of practice, and years of clinical experience. Odds ratios (ORs) and 95% confidence intervals (CIs) were reported.\u003c/p\u003e \u003cp\u003eAll analyses were performed using Python (v3.10) with appropriate statistical libraries (pandas, scipy.stats, and statsmodels).\u003c/p\u003e \u003cp\u003e \u003cb\u003eEthical Considerations\u003c/b\u003e \u003c/p\u003e \u003cp\u003e This study involved no patient-level data and did not require ethical approval under institutional guidelines for anonymous survey-based research. Participation implied consent, and respondents were informed of the anonymous nature of data handling and publication.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e \u003cb\u003eSurvey Participation and Respondent Characteristics\u003c/b\u003e \u003c/p\u003e \u003cp\u003eOf the 800 physicians invited to participate, 526 completed the survey, yielding a response rate of 65.8%. The respondents included 282 neonatologists (53.6%) and 244 pediatric cardiac intensivists (46.4%). Participants were geographically distributed across North America (58.6%), Europe (26.6%), and the Middle East (14.8%). Regarding clinical experience, 25.3% reported\u0026thinsp;\u0026lt;\u0026thinsp;5 years, 30.8% had 5\u0026ndash;10 years, 28.7% had 11\u0026ndash;20 years, and 15.2% had\u0026thinsp;\u0026gt;\u0026thinsp;20 years of experience. Slightly more than half of the respondents were female (53.2%). A summary of the demographic characteristics is presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e\u003cb\u003eDemographic Characteristics of Survey Respondents (\u003c/b\u003e\u003cem\u003eN\u0026thinsp;=\u0026thinsp;526)\u003c/em\u003e\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCategory\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003en\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSpecialty\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNeonatologist\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e282\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e53.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePediatric Cardiac Intensivist\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e244\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e46.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGeographic Region\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNorth America\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e308\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e58.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEurope\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e140\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e26.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMiddle East\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e14.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eYears of Experience\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;5 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e133\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e25.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u0026ndash;10 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e162\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e30.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11\u0026ndash;20 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e151\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e28.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;20 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e15.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSex\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e246\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e46.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e280\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e53.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eFever Management and Lumbar Puncture Practices\u003c/b\u003e \u003c/p\u003e \u003cp\u003eFever management approaches for neonates receiving PGE1 varied significantly by specialty. Pediatric cardiac intensivists were more likely to initiate a full sepsis work-up including antibiotics compared to neonatologists (65.6% vs. 38.7%, χ\u0026sup2; = 38.32, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Neonatologists more frequently opted for no work-up or partial work-up without antibiotics. Fever management strategies were not significantly influenced by region (χ\u0026sup2; = 17.79, p\u0026thinsp;=\u0026thinsp;0.120), sex (χ\u0026sup2; = 4.78, p\u0026thinsp;=\u0026thinsp;0.310), or years of experience (χ\u0026sup2; = 29.79, p\u0026thinsp;=\u0026thinsp;0.106).\u003c/p\u003e \u003cp\u003eLumbar puncture decision-making was not significantly different between the specialties (χ\u0026sup2; = 5.70, p\u0026thinsp;=\u0026thinsp;0.223). However, pediatric cardiac intensivists were more likely to perform LP based on laboratory findings or routine protocols, while neonatologists more often cited systemic signs or clinical deterioration. Differences in LP triggers were not statistically significant across region (χ\u0026sup2; = 20.79, p\u0026thinsp;=\u0026thinsp;0.139), sex (χ\u0026sup2; = 6.83, p\u0026thinsp;=\u0026thinsp;0.234), or experience (χ\u0026sup2; = 23.40, p\u0026thinsp;=\u0026thinsp;0.183). A detailed comparison of fever management and LP practices by specialty is presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eFever Management Practices by Medical Specialty\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1. Management Strategy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNeonatologists (n\u0026thinsp;=\u0026thinsp;282)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCardiac Intensivists (n\u0026thinsp;=\u0026thinsp;244)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSepsis Evaluation Approach\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFull sepsis work-up +\u0026thinsp;empiric antibiotics\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e109 (38.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e160 (65.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFull sepsis work-up, no antibiotics\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e45 (16.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e35 (14.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.660\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePartial work-up, no antibiotics\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e79 (28.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e76 (31.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.002*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo work-up\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e65 (23.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e89 (36.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLumbar Puncture Indications\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical deterioration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e46 (16.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e37 (15.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.723\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbnormal laboratory results\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e49 (17.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e56 (23.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.135\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSystemic signs of infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e53 (18.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e49 (20.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.709\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRoutine practice\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e56 (19.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e56 (23.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.412\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther indications\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e78 (27.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e46 (18.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.010*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cem\u003e*Statistically significant (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05)\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003ePredictors of Antibiotic Use and Full Work-up\u003c/b\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eAntibiotic Administration.\u003c/b\u003e Multivariate logistic regression identified specialty as a significant predictor of antibiotic administration. Pediatric cardiac intensivists had 3.07 times higher odds of initiating antibiotics for a febrile neonate receiving PGE1 compared to neonatologists (OR\u0026thinsp;=\u0026thinsp;3.07; 95% CI, 1.76\u0026ndash;4.40; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Sex, region, and clinical experience were not statistically significant predictors (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMultivariable Predictors of Empiric Antibiotic Administration\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePredictor Variable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOdds Ratio\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95% Confidence Interval\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpecialty\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCardiac Intensivist vs. Neonatologist\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e3.07\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e1.76\u0026ndash;4.40\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eClinician Sex\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale vs. Male\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.73\u0026ndash;1.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.878\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGeographic Region\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNorth America vs. Other regions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.86\u0026ndash;1.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.270\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eClinical Experience\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;10 years vs. \u0026lt;5 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.60\u0026ndash;1.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.806\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cem\u003e*Statistically significant (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05)\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eFull Sepsis Work-up.\u003c/b\u003e Similar results were found for the likelihood of performing a full sepsis work-up, with pediatric cardiac intensivists and clinicians from North America demonstrating significantly increased odds (OR\u0026thinsp;=\u0026thinsp;2.92; 95% CI, 1.74\u0026ndash;4.21; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Other variables were not significant.\u003c/p\u003e \u003cp\u003e \u003cb\u003eLumbar Puncture.\u003c/b\u003e No variables, including specialty, sex, region, or experience, were independently associated with LP performance in the multivariate analysis.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis cross-sectional survey reveals significant inter-specialty differences in the management of febrile neonates receiving PGE1 therapy. Our findings demonstrate that pediatric cardiac intensivists are substantially more likely than neonatologists to initiate full sepsis workups with empiric antibiotic therapy, with more than three-fold increased odds of antibiotic administration. These results highlight a critical gap in standardized care for this vulnerable population and underscore the need for evidence-based guidelines to optimize clinical decision-making.\u003c/p\u003e \u003cp\u003e \u003cb\u003eClinical Implications and Patient Safety Considerations\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThe substantial practice variation identified in our study raises important questions about optimal care for febrile neonates receiving PGE1. Both over-treatment and under-treatment may carry significant risks. Aggressive sepsis evaluation and empiric antibiotic therapy may lead to unnecessary invasive procedures, prolonged hospitalization, increased healthcare costs, and contribution to antimicrobial resistance. [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] LP in neonates with complex congenital heart disease may pose additional procedural risks, particularly in those with ductal-dependent circulation where hemodynamic instability could be precipitated by positioning or procedural stress. [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eConversely, conservative management risks missing life-threatening bacterial infections. Early-onset sepsis remains a leading cause of neonatal morbidity and mortality, with case fatality rates of 10\u0026ndash;15% for bacteremia and up to 25% for meningitis. [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] The immunocompromised state of critically ill neonates with congenital heart disease may further increase susceptibility to serious bacterial infections. [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThe absence of statistically significant differences in LP practices between specialties, despite differences in overall sepsis work-up approaches, suggests that both groups recognize the procedural risks and complexity of LP in this population. However, the variation in clinical triggers for LP (laboratory findings versus clinical deterioration) indicates ongoing uncertainty about optimal indications.\u003c/p\u003e \u003cp\u003e \u003cb\u003eFactors Influencing Practice Patterns\u003c/b\u003e \u003c/p\u003e \u003cp\u003eOur analysis revealed that demographic factors such as clinician sex, years of experience, and geographic region were not significant predictors of management decisions. This suggests that specialty-specific training and culture, rather than individual clinician characteristics, are the primary drivers of practice variation. The lack of regional differences is somewhat surprising given documented variations in antibiotic prescribing patterns and sepsis management protocols across different healthcare systems. [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThe absence of experience-related differences indicates that practice patterns are established early in specialty training and remain consistent throughout career progression. This finding supports the importance of evidence-based education and standardized protocols during residency and fellowship training programs.\u003c/p\u003e \u003cp\u003e\u003cb\u003e Toward Evidence-Based Guidelines\u003c/b\u003e\u003c/p\u003e \u003cp\u003e The substantial practice variation documented in our study underscores the urgent need for evidence-based guidelines specific to fever management in neonates receiving PGE1. Current pediatric sepsis guidelines do not address the unique clinical context of drug-induced fever in critically ill neonates with congenital heart disease. [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eSeveral strategies could help optimize care for this population. First, development of clinical prediction rules incorporating patient-specific factors (hemodynamic stability, biomarkers, duration of PGE1 therapy, etc.) could guide risk stratification and management decisions. [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] Second, implementation of standardized protocols that balance infection risk with the potential harms of over-treatment could reduce practice variation while maintaining safety. [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] Third, prospective studies examining outcomes associated with different management approaches could provide evidence to inform future guidelines.\u003c/p\u003e \u003cp\u003eRecent studies have begun to address this knowledge gap in managing fever in neonates receiving PGE1. Baranwal et al. conducted a prospective study demonstrating that presepsin may help differentiate between PGE1-induced systemic inflammation and true bacterial sepsis, offering a potential biomarker to reduce unnecessary antibiotic administration in this unique population. [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] Similarly, C-reactive protein and procalcitonin have shown utility in early-onset neonatal sepsis and may aid in distinguishing infectious from non-infectious causes of fever. [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] These biomarkers, when interpreted in the context of PGE1 therapy, could contribute to more nuanced decision-making and support a selective approach to antimicrobial use.\u003c/p\u003e \u003cp\u003e \u003cb\u003eFuture Research Directions\u003c/b\u003e \u003c/p\u003e \u003cp\u003eOur findings highlight several areas for future investigation. Prospective cohort studies examining clinical outcomes associated with different management strategies would provide critical evidence for guideline development. Additionally, research into biomarkers that can reliably distinguish PGE1-induced fever from infectious fever could revolutionize clinical decision-making in this population.\u003c/p\u003e \u003cp\u003eCost-effectiveness analyses comparing aggressive versus conservative management approaches could inform resource allocation and policy decisions. Finally, implementation studies evaluating the effectiveness of standardized protocols in reducing practice variation while maintaining patient safety would be valuable for healthcare systems seeking to optimize care quality.\u003c/p\u003e \u003cp\u003e \u003cb\u003eLimitations\u003c/b\u003e \u003c/p\u003e \u003cp\u003eSeveral limitations should be considered when interpreting our findings. First, the cross-sectional survey design captures reported practice patterns rather than actual clinical outcomes, limiting our ability to determine which approach leads to better patient outcomes. The clinical vignette methodology, while standardized, may not fully capture the complexity of real-world decision-making where multiple clinical factors influence management choices. Second, selection bias may have influenced our results, as physicians who chose to participate in the survey may differ systematically from non-respondents in their practice patterns or interest in evidence-based medicine. The 65.8% response rate, while reasonable for physician surveys, leaves open the possibility that non-respondents have different practice patterns. Third, our convenience sampling approach may not fully represent the broader population of neonatologists and pediatric cardiac intensivists. The geographic distribution of respondents, while spanning three continents, may not reflect global practice patterns, particularly in resource-limited settings where diagnostic capabilities and antibiotic availability may influence management decisions. Fourth, the survey instrument, despite pretesting and expert review, may not have captured all relevant clinical factors that influence decision-making in practice. Social desirability bias may have led some respondents to report practices that align with perceived best practices rather than their actual clinical behavior. Finally, our study did not collect data on institutional protocols or local guidelines that may influence individual clinician decision-making. Practice variation may be partially explained by differences in institutional culture and protocols rather than individual clinician preferences alone.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThis multinational survey demonstrates significant inter-specialty differences in the management of febrile neonates receiving PGE1 therapy, with pediatric cardiac intensivists substantially more likely to pursue aggressive sepsis evaluation and empiric antibiotic therapy compared to neonatologists. These findings highlight the absence of evidence-based guidelines for this clinical scenario and underscore the need for standardized approaches that balance infection risk with the potential harms of over-treatment.\u003c/p\u003e \u003cp\u003eThe substantial practice variation identified in our study represents a serious gap in pediatric healthcare that requires appropriate attention. Development of evidence-based clinical guidelines, informed by prospective outcome studies and validated risk stratification tools, is essential to optimize care for this vulnerable population. Such guidelines should incorporate specialty-specific perspectives while prioritizing patient safety and antimicrobial stewardship principles.\u003c/p\u003e \u003cp\u003eFuture research should focus on prospective studies examining clinical outcomes associated with different management strategies, development of biomarkers to distinguish infectious from drug-induced fever, and implementation of standardized protocols that can reduce practice variation while maintaining high-quality care. Only through such collaborative efforts can we ensure that neonates with life-threatening congenital heart disease receive optimal, evidence-based care during their most vulnerable period.\u003c/p\u003e "},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePGE1\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eProstaglandin E1\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCHD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCongenital heart disease\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eLumbar puncture\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgement:\u003c/strong\u003e None\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatement of Ethics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study involved no patient-level data and the institutional research board (IRB) exempted ethical approval under institutional guidelines for anonymous survey-based research. Participation implied consent, and respondents were informed of the anonymous nature of data handling and publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest Disclosures (includes financial disclosures):\u003c/strong\u003e All authors have no conflicts of interest to declare.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding/Support:\u0026nbsp;\u003c/strong\u003eThis study was not supported by any sponsor or funder.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDr. Sharon Morag conceptualized and designed the study, drafted the initial manuscript, and critically reviewed and revised the manuscript.\u003c/p\u003e\n\u003cp\u003eDrs. Alexander Lowenthal and Hiba Abuelhija designed the survey, designed the data collection instruments, collected data, carried out the initial analyses, and critically reviewed and revised the manuscript.\u003c/p\u003e\n\u003cp\u003eDr. Uri Pollak conceptualized and designed the study, coordinated and supervised data collection, and critically reviewed and revised the manuscript for important intellectual content.\u003c/p\u003e\n\u003cp\u003eAll authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe de-identified dataset supporting the conclusions of this article is available from the corresponding author (Dr. Uri Pollak, [email protected]) upon reasonable request for legitimate research purposes. Requests must include a detailed research proposal, institutional affiliation verification, and appropriate ethical approval where required. Data will be shared in standard formats with documentation, subject to conditions ensuring participant confidentiality, data security, and appropriate attribution of the original study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eFreed MD, Heymann MA, Lewis AB, Roehl SL, Kensey RC. Prostaglandin E1 infants with ductus arteriosus-dependent congenital heart disease. \u003cem\u003eCirculation\u003c/em\u003e. 1981;64(5):899\u0026ndash;905. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1161/01.cir.64.5.899\u003c/span\u003e\u003cspan address=\"10.1161/01.cir.64.5.899\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHeymann MA, Clyman RI. 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Serum procalcitonin as a diagnostic marker for neonatal sepsis: a systematic review and meta-analysis. \u003cem\u003eIntensive Care Med\u003c/em\u003e. 2011;37(5):747\u0026ndash;762. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00134-011-2174-8\u003c/span\u003e\u003cspan address=\"10.1007/s00134-011-2174-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-perinatology","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"jp","sideBox":"Learn more about [Journal of Perinatology](http://www.nature.com/jp/)","snPcode":"41372","submissionUrl":"https://mts-jper.nature.com/cgi-bin/main.plex","title":"Journal of Perinatology","twitterHandle":"@jperinatology","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Alprostadil, Fever, Infant, Newborn, Heart Defects, Congenital, Practice Patterns, Physicians', Anti-Bacterial Agents","lastPublishedDoi":"10.21203/rs.3.rs-7023048/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7023048/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eObjective\u003c/p\u003e\n\u003cp\u003eTo assess inter-specialty differences in the management of febrile neonates receiving prostaglandin E1 (PGE1) for duct-dependent congenital heart disease.\u003c/p\u003e\n\u003cp\u003eStudy Design\u003c/p\u003e\n\u003cp\u003eA cross-sectional, web-based survey was distributed to 800 neonatologists and pediatric cardiac intensivists in North America, Europe, and the Middle East. Respondents (n=526) were queried regarding their management of a clinical vignette involving a febrile neonate on PGE1, including decisions about sepsis work-up, antibiotic administration, and lumbar puncture. Data were analyzed using chi-square tests and multivariate logistic regression.\u003c/p\u003e\n\u003cp\u003eResult\u003c/p\u003e\n\u003cp\u003ePediatric cardiac intensivists were significantly more likely to initiate full sepsis work-up and antibiotic therapy (65.6% vs. 38.7%, p\u0026lt;0.001). Specialty was the only significant predictor of antibiotic administration (OR=3.07, 95% CI: 1.76–4.40, p\u0026lt;0.001). No significant differences were found in lumbar puncture practices.\u003c/p\u003e\n\u003cp\u003eConclusion\u003c/p\u003e\n\u003cp\u003eSignificant inter-specialty variation exists in the management of febrile neonates on PGE1, highlighting the need for evidence-based guidelines to standardize care and optimize antimicrobial stewardship.\u003c/p\u003e","manuscriptTitle":"Inter-Specialty Differences in the Management of Febrile Neonates on Prostaglandin E1","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-22 18:22:31","doi":"10.21203/rs.3.rs-7023048/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"revise","date":"2025-09-10T13:14:15+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"This content is not available.","date":"2025-09-01T21:21:04+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2025-09-01T14:57:10+00:00","index":3,"fulltext":"This content is not available."},{"type":"editorInvitedReview","content":"This content is not available.","date":"2025-08-01T18:53:40+00:00","index":2,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2025-07-19T22:24:49+00:00","index":2,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2025-07-17T22:19:31+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewersInvited","content":"","date":"2025-07-17T12:23:21+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-07-02T11:28:24+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-01T19:01:06+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Perinatology","date":"2025-07-01T19:01:05+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-perinatology","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"jp","sideBox":"Learn more about [Journal of Perinatology](http://www.nature.com/jp/)","snPcode":"41372","submissionUrl":"https://mts-jper.nature.com/cgi-bin/main.plex","title":"Journal of Perinatology","twitterHandle":"@jperinatology","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"ded6f2c1-be99-4aea-bb41-67e6a7d501d7","owner":[],"postedDate":"July 22nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":51692511,"name":"Health sciences/Risk factors"},{"id":51692512,"name":"Health sciences/Medical research/Outcomes research"}],"tags":[],"updatedAt":"2025-11-25T08:09:59+00:00","versionOfRecord":{"articleIdentity":"rs-7023048","link":"https://doi.org/10.1038/s41372-025-02512-w","journal":{"identity":"journal-of-perinatology","isVorOnly":false,"title":"Journal of Perinatology"},"publishedOn":"2025-11-24 05:00:00","publishedOnDateReadable":"November 24th, 2025"},"versionCreatedAt":"2025-07-22 18:22:31","video":"","vorDoi":"10.1038/s41372-025-02512-w","vorDoiUrl":"https://doi.org/10.1038/s41372-025-02512-w","workflowStages":[]},"version":"v1","identity":"rs-7023048","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7023048","identity":"rs-7023048","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}