EBNEO

Gabriel Altit from Canada www.theneocardiolab.com reviews the April Article of the Month "Mazhari MYA, Priyadarshi M, Singh P, Chaurasia S, Basu S. Norepinephrine versus Dopamine for Septic Shock in Neonates: A Randomized Controlled Trial. J Pediatr 2025;282:114599. https://doi.org/10.1016/j.jpeds.2025.114599. PMID 40252959." for ebneo.org. READ HERE! ACTA COMMENTARY: Acta Paediatrica - 2025 - Altit - EBNEO Commentary Review of the Norepinephrine Versus Dopamine for Septic Shock in.pdf "The randomized controlled trial by Mazhari et al. provides valuable comparative data on norepinephrine versus dopamine as first-line agents in neonatal fluid-refractory septic shock1. Despite these insights, several important limitations temper the interpretation of the findings. The study population included both term and preterm infants with a wide range of gestational ages and clinical presentations. The diagnosis of septic shock relied largely on clinical judgment, often in the absence of culture confirmation, with nearly half of participants classified as having “clinical sepsis.” This introduces a risk of misclassification bias and limits internal validity. Standardized sepsis scoring systems or objective definitions for endpoints such as “shock reversal” were not applied, raising concerns about subjectivity, particularly given the reliance on variable clinical signs such as capillary refill or pulse quality. The primary outcome—shock reversal within 30 minutes—may not be physiologically meaningful in neonates, where hemodynamic responses are dynamic and may evolve over a longer period2. Recruiting infants already in a decompensated state of shock likely contributed to the high mortality rate and may have hindered the ability to assess early treatment effects. The absence of echocardiographic assessment to characterize shock phenotypes is another key limitation. Neonatal septic shock is often hemodynamically complex, involving a mix of vasodilatory and cardiogenic features, sometimes exacerbated by persistent fetal shunts or elevated pulmonary vascular resistance2, 3. Without phenotypic stratification, it is difficult to determine whether either drug was more effective for specific shock subtypes. Methodologically, the trial used appropriate randomization and blinding strategies, but lacked standardization in critical aspects of drug delivery. Practical variables—such preparation site (bedside vs. pharmacy), carrier fluid use—were not described, which could introduce variability affecting drug efficacy. While the study measured cerebral regional oxygen saturation (CrSO₂), it did not report fractional tissue oxygen extraction (FTOE), which would have provided a more integrative index of oxygen delivery and utilization. Although CrSO₂ at 24 hours was significantly higher in the norepinephrine group (76.0 ± 7.3% vs. 69.5 ± 7.7%, p < 0.01), its clinical significance is unclear. CrSO₂ is influenced not only by perfusion but also by metabolic demand; higher values may reflect reduced cerebral metabolism rather than improved perfusion, potentially signaling adverse neurological effects4, 5. The study also suffers from the common pitfall of multiple unadjusted comparisons, increasing the risk of type I error. Without statistical correction strategies (e.g., Bonferroni adjustment or false discovery rate control), any significant secondary outcome must be interpreted with caution. Ideally, these findings should have been clearly framed as exploratory. Generalizability is another concern. All patients were enrolled at a single tertiary center in India, where microbial epidemiology and clinical practices differ from those in high-income settings. Pathogens were predominantly gram-negative, including Klebsiella pneumoniae, Acinetobacter spp., and E. coli, with no reported cases of Group B Streptococcus. The feasibility of conducting such a trial in this setting is commendable; however, the consent process (e.g., deferred or opt-out strategies) was not detailed, which is an important ethical consideration in acutely ill neonates. The average gestational age of participants was 33.2 weeks in both treatment arms, indicating that extremely preterm infants (<28 weeks’ gestation) were largely excluded. As such, the findings may not apply to this particularly vulnerable subgroup or to neonates with different underlying sepsis etiologies."

Narasimha Rao & H Gowda, from UK review the paper "Marlow N, Barrington KJ, ODonnell CPF, Miletin J, Naulaers G, Cheung PY, Corcoran JD, Khuffash E, Boylan GB, Livingstone V, Pons G, Straňák Z, Van Laere D, Macko J, Wiedermannova H, Dempsey EM; HIP consortium. Outcomes of extremely preterm infants who participated in a randomised trial of dopamine for treatment of hypotension (the HIP trial) at 2 years corrected age. Arch Dis Child Fetal Neonatal Ed. 2025 Jan 19:fetalneonatal-2024-327894. PMID: 39832819." for EbNeo.org. READ HERE! ACTA Commentary: Acta Paediatrica - 2025 - Rao - EBNEO Commentary Reevaluating Dopamine for Hypotension in Extremely Preterm Infants .pdf "Hypotension is common in extremely preterm infants, affecting nearly half of those weighing under 1000 g in the early postnatal period (1). However, there is no consensus on a definition, and thresholds for intervention vary widely. Many NICUs initiate treatment when mean arterial pressure (MAP) falls below gestational age in weeks (2). Dopamine is often used as first-line therapy and is effective in increasing MAP, though its long-term benefits remain uncertain (3,4). The Hypotension in Preterm Infants (HIP) trial was the first multicentre RCT to compare dopamine versus placebo in treating hypotension in infants under 28 weeks (5). The initial trial was stopped early due to recruitment challenges and found no significant difference in survival to 36 weeks without severe brain injury. The follow-up assessed 55 infants at 2 years of corrected age (6). Outcomes • Primary Outcome: Survival without neurodevelopmental impairment (NIDD) was 48% in the dopamine group compared to 25% in the placebo group (OR ~2.8, p=0.078). Although this difference was not statistically significant, the trend indicates potential benefits. • Secondary Outcomes: Rates of cerebral palsy, hearing or vision impairment, and Bayley-III cognitive and motor scores were similar across groups. However, dopamine-treated infants were significantly shorter and lighter at 2 years, raising concerns about growth suppression, potentially linked to dopamine’s known endocrine effects (7). These findings suggest that avoiding dopamine did not worsen neurodevelopmental outcomes in this small sample; however, a significant difference cannot be ruled out. The study raises two key clinical concerns: whether a restrictive approach may reduce survival without impairment, and whether dopamine may influence postnatal growth. Clinical Implications This study supports a nuanced approach to managing hypotension. In stable infants showing signs of adequate perfusion, the immediate use of dopamine can be safely deferred. The results emphasise the importance of evaluating systemic status (e.g., capillary refill, lactate, urine output) rather than focusing on an isolated BP value (8). However, the lower survival rate without impairment in the placebo group suggests that some infants might benefit from early inotropic support, indicating that a purely restrictive approach could be inadequate in specific cases. The observed growth impairment also requires clinical attention. Practitioners should consider monitoring both growth and endocrine function in infants exposed to dopamine. If future research confirms this effect, it could influence vasopressor choice and treatment thresholds. Conclusion The HIP trial follow-up underscores the complexity of managing hypotension in extremely preterm infants. While it does not provide definitive answers, it raises significant questions about long-term outcomes and emphasises the necessity for individualised care. Until larger trials offer clearer guidance, clinicians must carefully evaluate the potential benefits and risks of dopamine in the early neonatal period."

Mahmoud Abdelreheem & Hassanein Moustafa from UK review the paper 'Li Y, Wisnowski JL and Chalak L, et al. Mild hypoxic-ischemic encephalopathy (HIE): timing and pattern of MRI brain injury. Pediatr Res. 2022 Dec;92(6):1731-1736. doi: 10.1038/s41390-022-02026-7. Epub 2022 Mar 30. PMID: 35354930; PMCID: PMC9771796.' for EbNeo. Read Here! ACTA Commentary: Acta Paediatrica - 2025 - Abdelreheem - EBNEO Commentary Mild Hypoxic Ischemic Encephalopathy HIE Timing and Pattern of.pdf "Neonatal hypoxic-ischaemic encephalopathy (HIE) remains one of the leading causes of neonatal mortality and long-term disability worldwide. Infants with mild HIE, representing 50% of all HIE cases, are often perceived as low risk, with excellent prognosis and no long-term disability. However, recent studies have shown that one-quarter of infants with mild HIE have abnormal outcomes defined as death, motor impairment, or developmental delay at follow-up up to 18 months [1]. This study examines the evolution and spatial distribution of brain injuries on MRI in neonates with mild HIE. It addresses a significant gap in literature and has important implications for early diagnosis, prognosis, and treatment strategies. Brain parenchymal injury was present in 87 (61%) infants, and intracranial hemorrhage was observed in 60 (42%) infants. The authors recruited 142 neonates, although only 125 were included in certain analyses, likely due to incomplete imaging. This transparent reporting enhances the credibility of the findings by ensuring that the data analyzed were of high quality. This study highlights how subtle brain injuries evolve over time, confirming that early detection may allow for timely interventions [2, 3]. Moreover, this study explores brain injury patterns, revealing that even mild HIE can cause noticeable changes in brain structure. Identifying these patterns is vital, as it helps clinicians differentiate HIE-related changes from other neonatal brain pathologies. This informs clinical decisions, including whether to consider therapeutic hypothermia (TH) in borderline cases [4]. Additionally, the study’s use of advanced MRI techniques underscores the potential of neuroimaging as both a diagnostic and prognostic tool in neonatal care. However, the study has limitations, notably the small number of infants who did not receive TH, which may limit the generalizability of the findings. The authors also acknowledge variability in MRI protocols across institutions, the lack of EEG data, and potential selection bias toward initiating TH in more severely affected infants within the mild HIE spectrum. Notably, there have been no randomized controlled trials evaluating the efficacy of TH in mild HIE, and many centers continue to question its utility in this population. Clinically, the implications of this work are twofold. First, it emphasizes the need to monitor neonates with mild HIE, as subtle injuries may have long-term neurodevelopmental consequences. Second, it supports incorporating MRI into routine evaluation, facilitating identification of infants who could benefit from neuroprotective interventions. The findings also advocate for further studies to evaluate the efficacy of TH and other therapeutic agents, leading to individualized management strategies for affected infants [5, 6]. In summary, this study delivers a well-designed investigation that enhances our understanding of mild HIE. It lays the groundwork for future research aimed at optimizing the timing of neuroimaging and improving outcomes through early intervention. The study serves as a reminder that even mild insults to the neonatal brain warrant careful attention due to their potential to impact long-term development [7]. Future studies with larger cohorts and standardized imaging protocols are needed to confirm these observations and refine MRI timing in mild HIE cases."

Caitlin Eason, S. Christopher Derderian review the paper "Eaton S, Ganji N, Thyoka M, Shahroor M, Zani A, Pleasants-Terashita H, Ghazzaoui AE, Sivaraj J, Loukogeorgakis S, De Coppi P, Montedonico S, Sindjic-Antunovic S, Lukac M, Hamill J, Choo CSC, Nah SA, Hulscher J, Emil S, Petersen A, Wijnen R, Sloots C, Sigalet D, Kiely E, Svensson JF, Wester T, Pierro A. STAT trial: stoma or intestinal anastomosis for necrotizing enterocolitis: a multicentre randomized controlled trial. Pediatr Surg Int. 2024 Oct 29;40(1):279. PMID: 39470842." for EBNEO October 2024 Article of the Month. READ HERE! ACTA COMMENTARY: Acta Paediatrica - 2025 - Eason - EBNEO COMMENTARY Stoma or Intestinal Anastomosis for Necrotizing Enterocolitis.pdf "An estimated 42% of infants with NEC will require surgery for necrotic bowels. It was unknown whether resection with stoma creation or primary anastomosis resulted in better outcomes.1 The STAT trial compared the efficiency of intestinal recovery between these operative interventions and the primary outcome was parenteral nutrition (PN). Primary anastomosis following a resection remains low (15.8%) in patients with NEC, despite evidence that it is a suitable surgical intervention.2-5 However, it is difficult to evaluate retrospective studies due to inherent bias, because those receiving a primary anastomosis may be less sick than those requiring enterostomy. This trial aimed to minimize this bias by randomizing infants with NEC who could have reasonably had either operation. The STAT trial methodology highlights the challenges of comparing primary anastomosis to enterostomy, because the inclusion criteria were based on the subjective determination that either operation was appropriate. This compromised generalizability, because it depended on the surgeons’ judgement. Moreover, it is unclear why a surgeon would opt for a stoma when either operation was appropriate. It would be beneficial to obtain information about the surgeons’ decisions to perhaps establish protocols for such an ambiguous decision-making process. Furthermore, it took nearly a decade to recruit 79 patients across 10 centers. Details about those judged ineligible would have been valuable, but the baseline characteristics were similar between the groups. However, more patients in the stoma group required mechanical ventilation. The primary outcome, of PN duration, was predictably shorter in the primary anastomosis group, as intestinal continuity was maintained. PN is associated with several risk factors, including liver disease, electrolyte imbalances and central line-associated blood stream infections.6 These factors, and infant growth, were not evaluated as additional outcomes and may have provided clinically relevant support for anastomosis than simply PN duration. The main differences in secondary outcomes between the primary anastomosis and stoma groups were multiple intestinal complications and those related to the stoma. As expected, the stoma group had more stoma-related issues. Multiple intestinal complications were not explicit, making this difference rather obscure. We assumed that this higher rate of multiple complications indicated a more complex postoperative course. However, it was difficult to tell without knowing the combination of complications and the differences in additional abdominal operations. In addition, the study was probably underpowered to detect significant differences in secondary outcomes. Differences in intestinal complications and PN duration, in conjunction with similar mortality, support the need to evaluate length of stay. This could hypothetically be longer for the enterostomy group, due to the need for more healthcare resources for multiple complications and PN. The STAT trial findings support primary anastomosis in infants with NEC that require a laparotomy, if surgeons judge this to be safe and feasible. Such operations would probably reduce PN duration and decrease risks of multiple postoperative intestinal complications. Future research should focus on the parameters and protocols involved in these surgical decisions and evaluate the clinically significant results of such outcomes including infant growth, PN risks and length of stay."

Dyanne Ifeoma Imo-Ivoke, Joanna Preece review the paper "Katheria AC, El Ghormli L, Clark E, Yoder B, Schmölzer GM, Law BHY, et al. Two-Year Outcomes of Umbilical Cord Milking in Nonvigorous Infants: A Secondary Analysis of the MINVI Randomized Clinical Trial. JAMA Netw Open. 2024 Jul 1;7(7):e2416870. doi: 10.1001/jamanetworkopen.2024.16870. PMID: 38949814; PMCID: PMC11217871." for EBNEO. READ HERE! ACTA COMMENTARY: Acta Paediatrica - 2025 - Imo%E2%80%90Ivoke - EBNEO Commentary Two%E2%80%90Year Outcome of Umbilical Cord Milking in Nonvigorous Infants .pdf "Close to term, about a third of the fetal blood volume is within the placenta at any time.(1) At birth, blood flow in the umbilical vessels continues for some minutes, allowing the transfusion of blood within the placenta bed to the baby. This can transfer 20 – 30% of additional blood volume to the baby at birth and can be achieved by delayed (deferred) cord clamping, DCC or umbilical cord milking. DCC, which is cutting the cord after 60 seconds, is the preferred cord management method in all newborns. UCM offers similar benefits and is recommended for babies over 28 weeks GA (2) (not recommended in <28 weeks due to concerns of intraventricular haemorrhage). DCC and UCM offer benefits such as increased haemoglobin levels, less delivery room cardiovascular support and lower incidence of moderate-severe hypoxic-ischaemic encephalopathy compared to early (immediate) cord clamping. Most late preterm (GA between 34+0 and 36+6) and term babies are born in good condition and may only require an assisted transition. In some cases, babies may be born in poor condition, or the mother may require prompt lifesaving actions. In these cases, waiting for 60 seconds may not be possible, and the Resuscitation Council of UK supports milking the umbilical cord in babies >28 weeks GA.(3) The initial actions of drying and stimulating the baby, are parts of the newborn life support (NLS) and can be done while the baby is still attached to the cord. There is no clear evidence of the superiority of cord milking from an intact cord compared to the cut cord, but concerns exist about the effects of clamping the cord before the onset of respiration.(4) While the short-term benefits of DCC and UCM are widely known, there is not enough data on the long-term sequelae. This study is the largest RCT showing the long-term safety of UCM in babies born at > 35 weeks GA and improves our knowledge of the long-term safety of UCM. Also, it has a high follow-up rate, is a multicentre cross-over trial, thereby limiting bias5, and includes babies born in North America and Europe, making it a desirable study. This study has some limitations. Parental education plays a role in health outcomes and is variable in the population. However, most babies in this secondary analysis were born to parents with good school education, which can be a limitation when applying this to the general population. Waiver of consent for the primary trial but asking informed consent for the secondary analysis could have introduced some bias as most of the babies included in the secondary analysis had parents with higher educational level. Additionally, UCM is a low-cost intervention, and this study would be most beneficial to low-resource countries where more babies may be nonvigorous at birth due to poor antenatal care. With the study conducted in high-income academic centres where most mothers have sufficient prenatal care, applying this study to low-resource countries may be challenging as there may be different haemodynamic adaptations due to undetected chronic hypoxia."

David Rub & Elizabeth Foglia review EBNEO October 2024 Article of the Month: "Gallini F, De Rose DU, Iuliano R, et.al. Lung Recruitment Before Surfactant Administration in Extremely Preterm Neonates: 2-Year Follow-Up of a Randomized Clinical Trial. JAMA Netw Open. 2024 Sep 3;7(9):e2435347. doi: 10.1001/jamanetworkopen.2024.35347. PMID: 39320892; PMCID: PMC11425149." READ HERE! Discussed on the INCUBATOR PODCAST! ACTA COMMENTARY: Acta Paediatrica - 2025 - Rub - EBNEO Commentary Reassessing INSURE Is Lung Recruitment Necessary.pdf "Few therapies have impacted a field like surfactant has neonatology. Since its discovery in the 1980s, surfactant replacement therapy revolutionized the management of respiratory distress syndrome (RDS), reducing immediate associated mortality and subsequent development of bronchopulmonary dysplasia (BPD).(2) Historically, surfactant was delivered via endotracheal tube, followed by a prolonged course of invasive mechanical ventilation (IMV). However, as the link between prolonged IMV and development of BPD became more apparent, research efforts shifted to novel delivery methods to minimize IMV exposure. The original IMV-sparing technique is the intubate-surfactant-extubate (INSURE) method, which called for the immediate removal of the endotracheal tube following surfactant administration.(3) While newer methods of surfactant administration avoid an endotracheal tube altogether, either by using a thin catheter or supraglottic airway, INSURE remains the most commonly used method of surfactant administration in the US.(4–6) This study from Gallini et. al. presents the 2-year follow-up data from the IN-REC-SURE Trial, an unblinded, randomized control trial comparing the use of a recruitment maneuver prior to selective administration of surfactant to standard INSURE protocol.(7) The physiologic rationale for this study being that a “well-recruited” lung facilitates the homogenous distribution of surfactant and improves its efficacy.(8) Although the primary outcome did not show statistically significant differences between groups, the overall mortality benefit when including deaths during the NICU stay is striking (35.1% vs. 22.8%; P = 0.05). (7) However, it is important to note that statistical significance was only met in the per-protocol analysis. Of the 6 patients excluded from the ITT analysis (3 for meeting exclusion criteria post-enrollment and 3 who did not receive the assigned recruitment maneuver; all in the IN-REC-SURE arm) 4 died during their NICU stay. Furthermore, nearly 70% of infants in the trial received at least one sustained inflation (SI) during initial delivery room resuscitation. It has since been shown that exposure to SI in the delivery room increases risk of early mortality.(9) While the authors argued in the primary analysis of the IN-REC-SURE Trial (10) that this should not influence the results since infants in both groups received SI and there was no differential exposure, an increased baseline mortality risk may exaggerate the observed mortality benefit and may not be applicable to populations with lower baseline mortality risks. In considering the dissemination of this approach, clinicians must remain mindful of the technical demands, including the need for high-frequency ventilators and specific training to perform recruitment maneuvers safely. Despite these challenges, the study provides encouraging safety data regarding the IN-REC-SURE procedure with a possible signal for improved mortality. Future investigations, such as the proposed IN-REC-LISA Trial (11), should compare IN-REC-SURE with other commonly used less invasive strategies to further elucidate the optimal balance between effective lung recruitment and the benefits of avoiding endotracheal intubation to improve the outcomes of extremely preterm infants."

Harisa Spahic, Sandra P. Zoubovsky, & Robert Dietz review EBNEO February 2025 Article of the month: "Faix RG, Laptook AR, Shankaran S, Eggleston B, Chowdhury D, Heyne RJ, et al. Whole-Body Hypothermia for Neonatal Encephalopathy in Preterm Infants 33 to 35 Weeks’ Gestation: A Randomized Clinical Trial. JAMA Pediatr 2025; e246613. PMID 39992674." READ HERE! ACTA COMMENTARY: Acta Paediatrica - 2025 - Spahic - EBNEO Commentary Is Therapeutic Hypothermia Beneficial to Infants Born Between 33 and.pdf "HIE is a devastating pathology, resulting in significant morbidity and mortality1. TH is the currently the only effective treatment shown to reduce morbidity and mortality in term and late preterm infants with moderate to severe HIE 1,2. Despite the effectiveness of TH in infants >36 weeks, limited research has been conducted on the effects of TH for infants born at 35 weeks GA with even less at 33-34 weeks GA2–6. Faix and colleagues addressed this gap by conducting a randomized control trial across multiple centers assessing the effectiveness of TH in infants born at 33-35 weeks GA with moderate/severe HIE7. The results of this study demonstrate TH does not protect infants born at 33-35 week GA from death or disability when compared to normothermia. The ICE trial included 35-42 week infants and showed favorable results of TH8. Several small, single-center (primarily retrospective) studies have shown similar outcomes for term and preterm infants with moderate or severe HIE treated with TH3,4. Together, these studies prompted the American Academy of Pediatrics to recommend TH for infants “born at or greater then 35 weeks of gestational age”2. As a result, many centers have revised their criteria to include 35 week infants when considering TH for infants with HIE. However, one study has shown higher mortality for infants born at 34-35 week GA undergoing TH for HIE compared to term (> 37 weeks GA) infants5. Faix and colleagues astutely discuss that previous studies include small numbers of study participants at 35 weeks GA7. These data suggest that infants born at 35 weeks resemble those born at 33–34 weeks more than those ≥36 weeks7. Moreover, many studies have not stratified outcomes by gestational age, limiting clarity on who benefits most from therapeutic hypothermia. These findings call into question whether current AAP recommendations should be re-evaluated. Late preterm infants (33-36 weeks GA) have a relatively immature epidermal barrier and higher ratio of surface area to birth weight than term infants9, possibly contributing to higher cold stress involved in mortality and morbidity. Nevertheless, use of TH for preterm infants with HIE has been increasing6. Previous small-cohort studies and the current RCT underscore the need for further research and cross-institutional data sharing—guided by stakeholders—to clarify the role of therapeutic hypothermia and adjunctive therapies in infants born <37 weeks’ gestation. The variable findings from these studies may lead some providers alongside institutional stakeholders to consider an informed consent process with caregivers when considering TH for infants born at <36 weeks GA with moderate/severe HIE, providing an avenue to engage in shared decision making for this population. However, until guidelines like those published from the AAP are revisited, it may be difficult from a medical-legal perspective to alter practice in countries where guidelines suggest cooling infants <35 weeks. We strongly advocate for more research into the outcomes of 33–36 week GA patients (stratified by GA) with HIE who undergo TH to help inform the guidelines of national academies and individual practices."

Anup Katheria & Henry Lee review Knol R. et al's EBNEO December Article of the Month: "Knol R, Brouwer E, van den Akker T, DeKoninck PLJ, Onland W, Vermeulen MJ, de Boode WP, van Kaam AH, Lopriore E, Reiss IKM, Hutten GJ, Prins SA, Mulder EEM, d’Haens EJ, Hulzebos CV, Bouma HA, van Sambeeck SJ, Niemarkt HJ, van der Putten ME, Lebon T, Zonnenberg IA, Nuytemans DH, Willemsen SP, Polglase GR, Steggerda SJ, Hooper SB, Te Pas AB. Physiological versus time based cord clamping in very preterm infants (ABC3): a parallel-group, multicentre, randomised, controlled superiority trial. Lancet Reg Health Eur. 2024 Dec 4;48:101146. doi: 10.1016/j.lanepe.2024.101146. PMID: 39717227; PMCID: PMC11664066." READ HERE! ACTA COMMENTARY: Acta Paediatrica - 2025 - Katheria - EBNEO Commentary on Physiological Versus Time Based Cord Clamping in Very Preterm.pdf "Intact cord resuscitation has been described since the early 14th century where the umbilical cord would not be clamped until the lungs were aerated. (1) Since then, observational cohort studies suggested benefit of maintaining placental circulation during initial breathing steps. Subsequently, randomized controlled trials comparing intact cord resuscitation to either immediate cord clamping or shorter durations of delayed cord clamping have been conducted. The ABC3 trial is the largest randomized controlled trial to date comparing intact cord resuscitation to a shorter unsupported time-based cord clamping approach. The ABC3 trial attempted to use a patient centered approach to cord clamping whereby infants had their cord clamped once they reached a peripheral oxygen saturation of 85 percent while requiring less than 40 percent supplemental oxygen and had a heart rate of >100 beats per minute. However, the minimum time was at least 3 minutes, and the maximum time was 10 minutes before cord clamping occurred. If there was excessive maternal blood loss, the cord was clamped earlier as well. The mean time of cord clamping was just under 6 minutes in the intervention group. In 2024, the International Liaison Committee on Resuscitation (ILCOR) published a consensus on Science with treamtent recommendations for preterm infants. (2) The current ILCOR recommendations are summarized here: “While it is reasonable to consider [deferral of cord clamping for 120 seconds or more (long DCC)], the task force cannot recommend the long deferral for all infants based on this evidence. Instead, the long deferral could be considered only if there is no contraindication and if appropriate newborn stabilization can be provided on the intact cord (skilled team, proper training, appropriate equipment, enough space and ability to provide thermal management). More evidence is needed before recommending long DCC. Practicality, feasibility, cost-effectiveness, and equity issues need to be addressed.” The group of infants who had longer DCC and resuscitation initiated on the cord had lower average initial temperatures. It was noted that there was a positive impact of improved effect for outcomes based on experience of the team in providing the intervention. As with other aspects of neonatal resuscitation that require coordination amongst team members, practice, experience, and training in behavioral skills are likely to advance care with newer approaches of cord management. In this study, the authors have studied the effect of long DCC and promoting lung aeration compared to shorter durations of DCC. While there were no statistically significant differences in their primary outcome, there were a number of secondary benefits such as fewer red blood cell transfusions, less late onset sepsis. In additional family centered outcomes such as less anxiety from parents were noted. The authors mention that infants in this study are being followed for long term outcomes. It will be interesting to see the impact of PBCC on the neurodevelopment of these infants that had improved hemoglobin and less blood transfusions. Andersson et al demonstrated improved 4-year outcomes in term infants receiving 3 minutes of DCC compared to early cord clamping. (3) It is possible that preterm infants may have even greater benefits given their high risk of neurodevelopmental impairment."

READ HERE! @EBNEO ACTA COMMENTARY: Acta Paediatrica - 2025 - Uguru - EBNEO Commentary Non%E2%80%90Invasive HFOV Versus Nasal CPAP for Preterm Infants.pdf "The management of respiratory distress syndrome (RDS) in preterm infants is a critical aspect of neonatal care, and the choice of non-invasive ventilation strategies can significantly impact clinical outcomes. Among the various modalities available, Non-invasive High-Frequency Oscillatory Ventilation (NHFOV) and Nasal Continuous Positive Airway Pressure (NCPAP) have garnered attention for their roles in supporting preterm infants with varying degrees of RDS. Both techniques, each with distinct mechanisms and clinical implications, aim to support breathing and reduce the need for invasive ventilation, depending on indication. NHFOV employs rapid oscillatory pressures to enhance alveolar recruitment and improve gas exchange while providing continuous airway pressure. This maintains functional residual capacity and enhances ventilation-perfusion matching, potentially reducing the need for intubation [1]. Conversely, NCPAP delivers a constant pressure to keep the airways open, preventing atelectasis and supporting spontaneous breathing [2]. Both methods aim to minimize complications of mechanical ventilation, like ventilator-induced lung injury. Recent publication by Fitzgerald et al, comparing NHFOV and NCPAP suggests that NHFOV may offer advantages in terms of oxygenation and a lower incidence of bronchopulmonary dysplasia (BPD) [3]. This is particularly important given the long-term implications of BPD on neurodevelopmental outcomes. Fitzgerald et al suggested that NHFOV may lower intubation rates compared to NCPAP, particularly in very preterm infants or those with more severe respiratory distress, stating that NHFOV has been associated with a reduced need for intubation due to its effectiveness in providing respiratory support [3]. Likewise, reintubation rates can be influenced by the infant’s underlying condition. Some studies report that NHFOV might lead to lower reintubation rates compared to NCPAP, particularly in infants with evolving respiratory failure [1]. However, NCPAP remains a cornerstone of respiratory support in neonatal units, with an established safety profile and ease of application. Its lower cost and simplicity further contribute to its widespread use in neonatal units [4]. This systematic review and meta-analysis comparing Non-invasive High-Frequency Oscillatory Ventilation (NHFOV) and Nasal Continuous Positive Airway Pressure (NCPAP) for preterm infants [5], demonstrated that NHFOV significantly reduced the rate of intubation or reintubation compared to NCPAP, without increasing complications such as ventilator-induced lung injury. This corroborates insights from a growing body of literature. However, limitations of the study include the unblinded design, variations in sample size, gestational age, birth weight, and respiratory interfaces used across all included RCTs, which may affect the generalizability of the results. The authors recommend further multi-center research on a larger scale, incorporating subgroup analyses that account for differences in gestational age and birth weight, as this would provide a more comprehensive assessment of the effectiveness and safety of NHFOV. The choice between NHFOV and NCPAP should therefore consider clinical context, resource availability, and institutional protocols, including the infant’s condition and staff familiarity with each method. While NHFOV appears more effective in reducing intubation rates, both modalities have unique advantages and challenges in managing respiratory distress in preterm infants. As our understanding evolves, the goal remains to provide the safest and most effective respiratory support for our most vulnerable patients."

READ HERE! @EBNEO ACTA COMMENTARY: Acta Paediatrica - 2025 - Jayakumar - EBNEO Commentary Parent%E2%80%90Guided Developmental Intervention for Infants With Very Low.pdf Very preterm birth is associated with injury in the developing brain and subsequent impairments in cognitive, motor, behavioral and emotional skills.1,2 Early childhood provides a critical window for neurorestorative interventions, including developmental interventions, in the hospital and after discharge.3 Developmental interventions vary widely in their component elements, intensity, target domains, parental involvement, and cost. A majority of studies evaluating these interventions have been based in high-income countries.4 Given the heterogeneity of medical systems and access to follow-up care across the globe, results from prior studies may not be generalizable to low-to-middle-income (LMIC) countries. The randomized trial by Silveira et al, based in Brazil, addressed this critical gap and demonstrated that a parent-guided developmental intervention administered to high-risk preterm infants in a LMIC improved cognitive, language, and motor development through 18 months corrected age. Silveira, et al. observed a stronger effect of enhanced developmental support on motor outcomes compared to cognitive outcomes. While it is plausible that early motor developmental skills are more amenable to improvement with the study intervention, this finding is in contrast to many prior studies which show greater improvements in cognitive domains with early developmental intervention programs.5. Notably, the effect on motor skills strengthened between 4 and 18 months, suggesting a sustained or even increasing intervention effect over time. Strengths of this study include parental training beginning in the first week after birth and the assessment of numerous factors influencing neurodevelopment, including parents’ childhood experiences and socioeconomic status. Testing in the participants’ homes allowed for assessment of child neurodevelopment in a comfortable, familiar setting. The use of multiple scales measuring non-overlapping aspects of development allowed for a holistic evaluation of the child and their environment. The randomized design, use of blinded outcomes assessments, and robust sample size are additional strengths of the study. This study could have been further strengthened by inclusion of validated measures of infant state control, parent-infant bonding, parental mental health and self-efficacy. The Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), used to assess the primary outcome, is known to overestimate development.6,7,8, 9 Notably, the intensity of follow-up care provided to the control group is markedly higher than in many other settings, including some high-income countries. Therefore, similar interventions in settings with less robust follow-up might yield even greater effects and will be important to study the scalability of this intervention. While the authors acknowledge the burdens of extended follow-up, longer-term assessments will be essential for demonstrating persistence of intervention effects. Dr. Silveira’s trial represents an essential contribution to the literature describing the important impact of neurodevelopmental interventions on outcomes of high-risk infants and demonstrates the success of a parent-guided intervention in a LMIC. While LMICs are a varied group, the study offers a low-cost intervention that could be applied to numerous resource-limited settings, with potentially greater impact depending on the intensity of their follow-up services. This trial sets a benchmark for future studies of developmental interventions and provides a template for evidence-based developmental care of high-risk infants around the world.

READ HERE! @EBNEO ACTA COMMENTARY: Acta Paediatrica - 2025 - Neches - EBNEO Commentary Video Versus Direct Laryngoscopy for Urgent Intubation of Newborn.pdf Research on optimal neonatal intubation conditions often examines modifiable practices such as premedication, neuromuscular blockade, oxygen supplementation, and laryngoscopy type (e.g., video (VL) vs. direct (DL)). This single-center randomized study by Geraghty et al. focuses solely on laryngoscopy type while maintaining standardized premedication, including neuromuscular blockade. Key commentary opportunities include adverse intubation-associated events, the impact of standardized coaching during VL for trainees, and crossover data analysis. Intubation success and safety are closely linked, with adverse events occurring in approximately 20% of cases and ranging in severity (1). Less severe events include mainstem intubation, esophageal intubation with immediate recognition, emesis without aspiration, hypertension, epistaxis, medication error, dysrhythmia, pain, and gum/lip/oral trauma. Severe events include cardiac arrest, hypotension requiring intervention, pneumothorax/pneumomediastinum, direct airway injury, esophageal intubation with delayed recognition, laryngospasm, malignant hyperthermia and emesis with aspiration (1). Increased intubation attempts correlate with higher adverse event rates (2-4), underscoring the importance of addressing tracheal intubation-associated events to optimize outcomes. While this study monitored heart rate, oxygen saturation, and the need for chest compressions or epinephrine, other adverse events were not assessed. Among 198 intubations, 6% of VL cases and 5% of DL cases involved cardiac arrest requiring chest compressions, with three deaths occurring across both groups. In comparison, a study from a large international airway registry of over 2700 intubations reported rare rates of chest compressions – 0.6% for VL and 1% for DL (5). Although underpowered to detect adverse event patterns, the current study raises important questions about rates of severe adverse event rates and whether specific factors in infants requiring advanced resuscitation merit further investigation. The use of VL for training is well-documented (6-9), with growing evidence highlighting the benefits of coaching, teaching, and simulation. Shared airway visualization with a senior provider or coach may enhance experience, competence, and confidence and result in educational impact across different trainee experience levels. Given the two-year study period, analyzing month-to-month trainee success could clarify whether skills improved over time and amplify the impact of VL on skill acquisition and patient outcomes. Incorporating quality improvement tools like Statistical Process Control charts may add valuable insights. This randomized clinical trial (RCT) employed an intention-to-treat approach, analyzing participants based on their original group assignments regardless of crossover. Crossover, where participants switch groups, complicates analysis, dilutes treatment effects, and obscures the true impact. Intention-to-treat analysis reflects real-world treatment performance and reduces bias. In this study, 3% of participants crossed over from VL to DL, while 29% switched from DL to VL, potentially influencing results. While this crossover may have occurred in the setting of provider preferences or technical challenges, the impact of the crossover may be an underestimation of the benefits of VL. Given the multifactorial approach to neonatal intubation, subgroup and post-hoc analyses could clarify the impact of provider and practice variables on procedural success. Including indication for intubation may highlight success and safety profiles related to various procedural practices and patient populations. For instance, premedication practices affecting intubation success may differ between patients needing Intubation-Surfactant-Extubation (INSURE) and those requiring prolonged mechanical ventilation. In the future, the safety and success of neonatal intubation may be further enhanced by implementing tailored protocols that provide specific guidance on premedication, types of laryngoscopy, oxygen provision during intubation, and standardized intubation checklists. These protocols may be based on individual patient needs or the specific indication for intubation. Additionally, strategies could be developed to address the unique requirements of the intubating provider, such as a “first-year doctor in training” protocol or an “emergency re-intubation” approach for an attending neonatologist managing a patient with a difficult airway. These efforts could further optimize outcomes by aligning techniques and resources with both patient and provider considerations.

Dustin Beyer and Hans Proquitté review the paper "Lowe, J., Gillespie, D., Aboklaish, A., Lau, T. M. M., Consoli, C., Babu, M., Goddard, M., Hood, K., Klein, N., Thomas-Jones, E., Turner, M., Hubbard, M., Marchesi, J., Berrington, J., & Kotecha, S. (2024). Azithromycin therapy for prevention of chronic lung disease of prematurity (AZTEC): a multicentre, double-blind, randomised, placebo-controlled trial. The Lancet. Respiratory medicine, 12(8), 608–618. PMID: 38679042." for EBNEO & Acta Paediatrica. READ HERE! Acta Commentary: Acta Paediatrica - 2024 - Beyer - EBNEO Commentary Azithromycin therapy for prevention of chronic lung disease.pdf The findings of the AZTEC trial can be contextualized within the broader landscape of current developments in neonatology, regarding the area of chronic lung disease (CLD). This trial investigated whether or not early intravenous azithromycin improves survival without moderate or severe BPD in preterm infants, irrespective of the Ureaplasma colonization. In recent years, there have been several other major trials evaluating interventions to prevent CLD in preterms. A notable example is the trial by Watterberg et al., which examines the role of hydrocortisone on CLD-free survival in preterm infants less than 30 weeks’ gestation. (1) This study, along with the AZTEC trial, highlights the continued challenge of exploring effective strategies to overcome this complex, multifactorial health burden. Interestingly, Azithromycin treatment does not improve the overall outcome of preterm infants regarding CLD-free survival. These findings strongly contradict the results of multiple studies published recently. The lack of a significant effect within the AZTEC trial is consistent with the results of a 2021 systematic review by Razak and Alshehri, which also could not show a significant reduction of CLD rates and death by azithromycin treatment. This is of interest, as those preterm infants colonized with Ureaplasma spp. could significantly benefit in terms of decreased rate of BPD and death. (2) A limitation regarding this secondary outcome is the relatively small number of preterm infants colonized with Ureaplasma compared to the overall study population. In contrast, the AZTEC trial implemented a distinctive azithromycin dosing regimen compared to previous randomized controlled trials. The protocol consisted of 20mg/kg for the first three days – a dose known to eradicate respiratory Ureaplasma colonization – followed by 10mg/kg for additional seven days to may benefit from anti-inflammatory properties. (2) Two landmark studies by Ballard et al. used a longer, 6-week azithromycin course. This significant variation in treatment duration makes direct comparison of results challenging. (3, 4) Interestingly, the AZTEC trial found a reduction in the rate of treated ROP in survivors receiving azithromycin, although this effect was missing if mortality was included. This observation is engaging, as it suggests a potential secondary benefit of the intervention, possibly related to reduced oxygen requirements or systemic inflammation. Further investigation of this finding could provide insights of possible interactions of azithromycin with the progression or deterioration of ROP. In this context, the AZTEC trial emphasizes the need for a more comprehensive, multifaceted approach to prevent and manage CLD in preterm infants born before 30 weeks’ gestation. The trial demonstrates that there is no evidence supporting the routine use of azithromycin for CLD prevention in preterm infants. Future research, as suggested by the authors, should focus on evaluating azithromycin specifically in Ureaplasma-colonized preterm infants, potentially employing novel intervention combinations and innovative trial designs to address this persistent challenge in neonatal care. (5, 6)

Dr Kiran Shrivastava from Mumbai and Dr Abdul Razak from Australia review Sotiropoulos JX et al's #EBNEO June Article of the month: "Sotiropoulos JX, Oei JL, Schmölzer GM, Libesman S, Hunter KE, Williams JG, Webster AC, Vento M, Kapadia V, Rabi Y, Dekker J, Vermeulen MJ, Sundaram V, Kumar P, Kaban RK, Rohsiswatmo R, Saugstad OD, Seidler AL. Initial Oxygen Concentration for the Resuscitation of Infants Born at Less Than 32 Weeks’ Gestation: A Systematic Review and Individual Participant Data Network Meta-Analysis. JAMA Pediatr. 2024 Aug 1;178(8):774-783. doi: 10.1001/jamapediatrics.2024.1848. PMID: 38913382; PMCID: PMC11197034" READ HERE! Hear it discussed on the Incubator Podcast as well! Acta Commentary: Acta Paediatrica - 2024 - Shrivastava - EBNEO Commentary Comparing delivery room oxygen for preterms An IPD NMA Review.pdf The Individual Participant Data and Network Meta-analysis (IPD-NMA) examined 11 of 13 eligible studies, including data from 1003 babies, to address a critical question in neonatal care: What is the optimal initial oxygen concentration for resuscitating preterm infants born at less than 32 weeks' gestation? The authors categorised initial oxygen concentrations into three groups: low (21%–30%), intermediate (50%–65%), and high (90%–100%). They found that high initial oxygen concentrations were associated with a reduction in death compared to low and intermediate concentrations. Furthermore, they observed no differences in secondary outcomes, except for higher oxygen saturation within 5 min in the high oxygen group compared to the low oxygen group.1 These findings stand in contrast to previously conducted meta-analyses, which showed no significant effect of initial oxygen concentration on mortality. These earlier analyses typically compared low versus high oxygen concentrations based on an arbitrary distinction classifying infants exposed to intermediate oxygen as part of the high oxygen group. This categorisation likely diluted the apparent lower effect of high oxygen on mortality, ultimately leading to conclusions of no significant difference.2-4 In contrast, the IPD-NMA categorises oxygen exposure more precisely, revealing a significant reduction in mortality with high oxygen compared to both low and intermediate exposures. The striking impact of brief differences in initial oxygen exposure on such a critical outcome might prompt immediate consideration of this approach in clinical practice. However, it is essential to carefully weigh the certainty of this evidence, which remains low to very low. This lower certainty is driven by several factors, most notably statistical heterogeneity. In NMA, prediction intervals serve as a measure of heterogeneity and are based on the posterior distribution of analysis. They tell us that, with 95% certainty, the effect of a new trial would fall within this range. The authors point out that the lower mortality seen with high oxygen levels becomes nonsignificant as the prediction intervals cross the null, suggesting significant heterogeneity and reducing our confidence in the result. This statistical heterogeneity may, at least in part, be influenced by differences in how oxygen was titrated in the included trials (clinical heterogeneity). Most trials employed slow titration, while others used fast titration, and one trial even increased oxygen concentration from 0.21 to 1.0 rapidly. Such variations in oxygen delivery methods likely contributed to the observed heterogeneity.1 Additionally, the trials enrolled infants over a span of the last two decades and involved populations from different countries, further contributing to the variability. Beyond heterogeneity, other factors, such as the lack of blinding in many trials and the relatively low numbers of participants leading to imprecise estimates, also diminish confidence in the findings and raise questions about their overall reliability. While this type of IPD-NMA provides more credible evidence compared to traditional pairwise meta-analyses, the above-mentioned concerns urge caution among neonatal care providers. Should we adopt this evidence from a meta-analysis of heterogenous trials examining 1003 infants, or should we wait for more homogenous clinical trials with larger populations, such as the TORPIDO (Targeted Oxygen saturation in Respiratory care of premature Infants at Delivery: effects on Outcome) trial (1470 participants) and the HILO (higher versus lower oxygen) trial (1200 participants)?5, 6 This is just the beginning of our journey to determine the best approach to oxygen use in preterm resuscitation. Ongoing studies like OPTISTART (Optimisation of Saturation Targets And Resuscitation) may further illuminate how to optimise oxygen therapy after birth for these vulnerable infants.7

Ashlee Smith-Patel, Daniela Dinu & Elena Itriago from Baylor College of Medicine, Houston, TX, United States review Wei et al's paper: "Wei X, Franke N, Alsweiler JM, Brown GTL, Gamble GD, McNeill A, Rogers J, Thompson B, Turuwhenua J, Wouldes TA, Harding JE, McKinlay CJD; pre-hPOD Early School-age Outcomes Study Group. Dextrose gel prophylaxis for neonatal hypoglycaemia and neurocognitive function at early school age: a randomised dosage trial. Arch Dis Child Fetal Neonatal Ed. 2024 Jun 19;109(4):421-427. doi: 10.1136/archdischild-2023-326452. PMID: 38307710; PMCID: PMC11186727" for EbNeo. READ HERE! Acta Commentary: Acta Paediatrica - 2024 - Smith%E2%80%90Patel - EBNEO commentary Dextrose gel prophylaxis for neonatal hypoglycemia and.pdf Neonatal hypoglycemia is a common condition. Symptomatic neonatal hypoglycemia has been associated with white matter injury on brain magnetic resonance imaging, and even transient or undetected hypoglycemia may be associated with impaired executive functioning in early childhood.1, 2 This has led to studies evaluating prophylactic use of dextrose gel to decrease the incidence of hypoglycemia and, potentially, the incidence of neurodevelopmental impairment (NDI) later in life.3, 4 In this study, the authors were able to follow up and assess 80% of the initial cohort from the pre-hPOD trial,4 which compared various dextrose gel dosages (200 mg/kg, 400 mg/kg, 800 mg/kg, 1000 mg/kg) administered prophylactically at one hour of life with placebo. A previous analysis of the same cohort at two years of age found no difference in the composite neurosensory impairment outcome between placebo and dextrose gel,5consistent with another trial (the hPOD trial) which also compared the neurodevelopmental outcome at two years for infants born at risk and found no significant difference between 200 mg/kg 40% dextrose gel and placebo, but was underpowered to detect small but potentially clinically relevant differences in neurosensory impairment.6 The investigators evaluated multiple domains (neurocognitive function; visual perception; reading; numeracy, body size and composition; and grip strength) and found no difference in the primary outcome of cognitive impairment at 6–7 years of age for children randomised to various doses of prophylactic dextrose gel compared with control. When sample size was increased by combining all those exposed to intervention there was a lower risk of motor impairment (3% vs. 14%) and higher mean (SD) cognitive scores (106.0 (15.3) vs. 101.1 (15.7). These findings support the hypothesis that certain higher-order cognitive functions may not be fully developed at younger ages, and longer follow-up might be needed to detect poor executive function or visual impairment.3 The improvement in the motor skills at 6–7 years of age in this study which contrasts with previous reports may be due to the poor predictive value of the neurological exam and Bayley exam performed at 2 years of age in predicting motor skills later in childhood.7 However, it should also be considered that a limitation of this study were differences in baseline characteristics, with the children who were assessed being more likely to be born to older and more educated mothers, compared to those children lost to follow-up. The placebo group had a high rate of neurocognitive impairment (56%), compared with the dextrose group (48%). These results supports the hypothesis that the prophylactic gel prevented episodes of hypoglycemia that went undetected with intermittent sampling, as shown by studies using continuous glucose monitoring.2 While there were no identified adverse effects associated with the use of prophylactic dextrose gel, the number needed to treat (NNT) to prevent one case of NDI would likely be high, considering that the initial trial showed an NNT of 21 to prevent one case of hypoglycemia and larger studies.6 More studies are needed to evaluate benefits, harms, timing and dosing of prophylactic treatment in infants at risk of developing hypoglycemia.

Danielle Barber and Jill Chang from University of Colorado/ Children’s Hospital of Colorado review EbNeo August Article of the month: Nangle AM, He Z, Bhalla S, Bullock J, Carlson A, Dutt M, Hamrick S, Jones P, Piazza A, Vale A, Sewell EK. Reducing the percentage of surviving infants with acute symptomatic seizures discharged on anti-seizure medication. J Perinatol 2024. PMID 39043995 READ HERE! Acta Commentary: Acta Paediatrica - 2024 - Barber - EBNEO commentary Reducing the percentage of surviving infants with acute symptomatic.pdf.download.zip There is strong guidance to discontinue antiseizure medications (ASMs) prior to hospital discharge for neonates with acute symptomatic seizures. In the 2023 International League Against Epilepsy (ILAE) Task Force on Neonatal Seizures published guidelines,1 one of the six main recommendations is that ‘following cessation of acute provoked seizures without evidence for neonatal-onset epilepsy, ASMs should be discontinued before discharge home, regardless of magnetic resonance imaging or electroencephalographic findings’. Additionally, a comparative effectiveness study found no difference in neurodevelopmental impairment or epilepsy rates at 24 months among children whose ASM was discontinued vs. maintained at hospital discharge.2 While these recommendations have become stronger with time, they are not new: it has been more than a decade since the 2011 WHO Guidelines on Neonatal Seizures advised considering discontinuation of ASMs in neonates who had been seizure-free for 72 h.3 Despite these strong recommendations, there remains variation in clinical practice.4-7 The intuitive bias—particularly in centres without in-person neurology to evaluate the infant during the NICU hospitalisation—is that the ‘safer’ approach is to maintain the infant on ASMs until they see a neurologist in clinic. However, unnecessary ASM may contribute to long-term cognitive impairment8 and does not diminish the risk for future seizures.2, 4, 6 Inclusion of standardised treatment pathways for management of neonatal seizures has been shown to reduce the number of infants discharged home on ASMs. In the ILAE Task Force on Neonatal Seizures, 80% of experts surveyed ‘completely agreed’ and the remaining 20% of experts ‘mostly agreed’ that ‘a standardized treatment pathway for the management of neonatal seizures should be available in each neonatal unit’.1 Across hospitals with neonatal seizure treatment pathways, there is broad agreement on much of the treatment approach, including early discontinuation of ASMs.9 In Nangle et al., the authors describe the initiation of a neonatal seizure pathway in three hospitals where it did not previously exist and found ~50% reduction in infants discharged on ASMs in the subsequent epoch. Notably, the authors even reached 0% of infants with acute symptomatic seizures discharged on ASMs in 2023 at their Delivery Hospitals. We would like to particularly highlight that the authors of this study demonstrated feasibility and meaningful improvement in hospitals without in-person neurology consult availability. In fact, although possibly confounding by disease severity and seizure burden, fewer infants were discharged on ASM in the hospitals without neurology consult compared to the NICU with neurology consultation available. Additionally, their success highlights the benefits of working in multidisciplinary teams—both across various types of clinicians and partnerships between neonatology and neurology.