The research, led by Sophie Tribolet and Vincent Rigo of the neonatology division at University Hospital of Liège, together with a large team of collaborators across the country, drew on data from the SUPREMEneo prospective cohort. In June 2024, the investigators captured every laryngoscopy performed in all 19 neonatal intensive care units in Belgium, making it an exhaustive national snapshot rather than a sample from a handful of willing centers. The analysis focused on 142 laryngoscopies: 91 were performed to intubate newborns for mechanical ventilation, and 51 were performed to administer surfactant through a less invasive technique known as LISA, or less invasive surfactant administration, which has become the preferred approach for many preterm infants with respiratory distress syndrome. Fourteen of the intubations occurred in immediate life-threatening situations, where speed understandably takes precedence over comfort.

The headline numbers are sobering. Premedication was given before 56 of 77 non-emergency intubations, a rate of 73 percent, and before 35 of 51 LISA procedures, a rate of 69 percent. In other words, roughly three in ten elective, non-urgent laryngoscopies were carried out on unsedated newborns. The study also identified exactly where and when the practice falters. Premedication was significantly less likely when intubation was urgent, defined as needing to happen within ten minutes, and when the procedure took place in the delivery room rather than in the neonatal unit. For LISA procedures, no such delivery room penalty appeared, suggesting that the gap is not simply about location but about the perceived urgency and logistics surrounding intubation specifically.

Who performs the procedure also matters, in ways that differ between the two types of laryngoscopy. For LISA, premedication rates varied according to the operator’s professional status and their previous laryngoscopy experience, with statistical significance at p equal to 0.04 and 0.05 respectively. For intubation, the rates differed according to whether the operator had previously performed a successful laryngoscopy, at p equal to 0.01, but not according to operator status. These patterns hint at a cultural and educational dimension: clinicians who are more experienced, or more confident, may be more comfortable taking the extra minutes needed to sedate a baby, while those under pressure or in training may default to proceeding without drugs.

The pharmacology itself revealed remarkable heterogeneity. There was no single standard regimen across the country. The most commonly used drug was propofol, a short-acting anesthetic agent that provides rapid sedation but requires careful monitoring of blood pressure and breathing. Atropine, a drug given to protect against the slowing of heart rate that laryngoscopy can provoke, was administered before 37 of 128 non-life-threatening procedures, or 29 percent. Interestingly, atropine was given far more frequently in combination with fentanyl, an opioid, with or without a muscle relaxant, than alongside propofol, a difference that was highly statistically significant. This split reflects two competing philosophies of neonatal premedication: one favoring anesthetic agents with predictable short duration, the other favoring analgesia-based combinations with cardiovascular protection.

Perhaps the most actionable finding concerned protocols. Units that had a specific written premedication protocol behaved very differently from those without one. In units without protocols, 70 percent of non-emergency intubations and a staggering 90 percent of LISA procedures went ahead without premedication. In units with protocols, those figures fell to 24 percent and 53 percent respectively, differences that were statistically significant. The message is blunt: simply having a protocol, even before considering what it says, dramatically changes behavior. Standardization appears to convert premedication from an individual judgment call, vulnerable to habit and time pressure, into a default practice that clinicians must actively decide to bypass.

The researchers also asked clinicians why they skipped premedication, and the answers paint a nuanced picture. In 24 percent of unsedated laryngoscopies, the stated reason was the perception that the infant was comfortable or did not need it, a judgment that the authors implicitly challenge given the well-documented physiological stress response to laryngoscopy. Lack of venous access accounted for 19 percent of cases, a genuine practical obstacle in tiny premature infants whose veins are difficult to cannulate, though it raises questions about whether alternative routes or timing of line placement could help. Unit protocol was cited in 16 percent of cases, implying that some existing protocols may themselves be inadequate or permissive of omission, and personal habits accounted for 11 percent, an admission that routine rather than reasoning drives some decisions.

The context for these findings is a decade-long international debate. The American Academy of Pediatrics and the Canadian Paediatric Society both recommend premedication before elective neonatal intubation, and the French Neonatology Society has issued similar guidance. Yet audits in multiple countries have repeatedly shown that adherence lags far behind the recommendations. Part of the hesitation stems from legitimate clinical concerns: premedication drugs can cause hypotension, prolong the procedure if the baby becomes too sedated, and in the case of muscle relaxants, leave the infant apneic and dependent on the operator’s skill to secure the airway quickly. In units where operators have variable experience, these risks can feel more immediate than the longer-term harms of pain. The Belgian data showing that operator experience correlates with premedication rates suggests these concerns are being weighed differently by different hands at the bedside.

The stakes extend beyond the moment of discomfort. Repeated painful procedures in the neonatal period have been associated in longitudinal research with altered pain processing, differences in brain development, and poorer neurodevelopmental outcomes, although the evidence base for the benefits of any specific premedication regimen remains incomplete, which is itself part of why practice varies so widely. LISA, which avoids intubation and mechanical ventilation in many preterm infants, was developed partly to reduce procedural burden, but it still requires the same laryngoscopy to visualize the glottis and pass a thin catheter, so the pain problem does not disappear with the gentler technique. The Belgian study’s finding that 90 percent of LISA procedures in protocol-less units were done without premedication indicates that the shift toward less invasive surfactant delivery has not automatically carried analgesia with it.

The authors conclude that substantial inter-center variability persists, and that the development and implementation of premedication protocols may improve compliance and ultimately enhance the quality and safety of laryngoscopies in newborns. Because the study captured every NICU in a single country over a defined month, it offers an unusually complete picture of the gap between guideline and bedside, and its protocol findings provide a concrete lever for change: units seeking to improve need not wait for new drugs or new evidence, but can start by writing down, agreeing on, and enforcing a standard approach. For the smallest patients, who cannot advocate for themselves and whose pain is easy to underestimate, that administrative act may be one of the simplest available protections.

Subject of Research: Premedication practices before neonatal laryngoscopy in neonatal intensive care units

Article Title: Premedication practices prior to neonatal laryngoscopy: a nationwide observational study in Belgian NICUs

Article References: Tribolet, S., Legros, L., Laval, N., Derriks, F., Naessens, P., Debuf, M.-J., Van Poucke, J., Godart, V., Guevorkian, D., Schögler, A., Perceval, C., Ceulemans, L., Reibel, R., Plaskie, K., Debeer, A., Hocq, C., Rohaert, C., Avino, D., De Buyst, J., … Tauzin, M. (2026). Premedication practices prior to neonatal laryngoscopy: a nationwide observational study in Belgian NICUs. BMC Pediatrics. https://doi.org/10.1186/s12887-026-07813-3

Image Credits: AI Generated

DOI: 10.1186/s12887-026-07813-3

Keywords: neonatology, laryngoscopy, premedication, intubation, LISA, surfactant, NICU, propofol, pain management, preterm infants, clinical protocols, Belgium

Tracheal intubation, the placement of a tube into the windpipe to secure an infant’s airway, is among the highest-stakes procedures performed on newborns. It requires a clinician to thread a tube through the vocal cords of a patient who may weigh less than a kilogram, often while that patient is critically ill. The procedure is known to carry a substantial burden of adverse events, including oxygen desaturation, bradycardia, and in rare but devastating cases, cardiac arrest. Because newborns have a predominantly parasympathetic cardiovascular system, their hearts are especially vulnerable to vagal stimulation, which can be triggered by laryngoscopy and airway manipulation, slowing the heart rate dangerously.

Atropine works by blocking acetylcholine receptors at the muscarinic sites of the heart, effectively dampening the vagal reflexes that can cause the heart to slow. The logic behind its use during intubation has been straightforward: if airway manipulation can provoke reflex bradycardia, and if severe bradycardia can cascade into cardiac arrest, then preemptively blunting that reflex should protect the infant. That reasoning, drawn largely from pediatric anesthesia and emergency medicine, has made atropine a standard component of premedication regimens in neonatal units around the world, alongside sedatives and, in some centers, neuromuscular blocking agents.

To test that assumption at scale, a team led by Taylor Sawyer of the University of Washington School of Medicine and including co-senior authors Elizabeth Foglia and Akira Nishisaki turned to the NEAR4NEOS registry, an international collaborative that prospectively collects standardized data on every intubation attempt at participating neonatal units. The researchers analyzed 13,085 neonatal tracheal intubations performed between 2014 and 2023, making this one of the largest datasets ever assembled to examine the safety of neonatal airway management. Atropine was administered in 8,189 of those procedures, or 62.6 percent, underscoring just how deeply entrenched the practice is.

The team used multivariable logistic regression to compare outcomes between intubations in which atropine was given and those in which it was not, adjusting for confounding factors such as patient characteristics and clinical context. The primary outcome was cardiac arrest during the procedure. The result was striking: atropine use was not associated with reduced odds of cardiac arrest, with an adjusted odds ratio of 0.52 and a confidence interval spanning from 0.25 to 1.09, a range that crosses the threshold of statistical significance. In other words, the data could not demonstrate that the drug prevents the very complication it is most often given to avert.

The secondary findings were equally revealing. Atropine did deliver on one of its promised effects: it was associated with substantially lower odds of severe bradycardia, with an adjusted odds ratio of 0.33, meaning the drug cut the risk of dangerous heart rate slowing by roughly two-thirds. But that cardiac benefit came with trade-offs. Infants who received atropine had higher odds of oxygen desaturation during the procedure, with an adjusted odds ratio of 1.35, and lower odds of success on the first intubation attempt, with an adjusted odds ratio of 0.76. First-attempt success matters enormously in neonatal care, because repeated attempts prolong airway manipulation, increase physiological stress, and compound the risk of harm.

The desaturation finding has a plausible physiological explanation. Atropine increases heart rate and cardiac output, which can accelerate the consumption of oxygen reserves in an infant whose lungs are being ventilated intermittently or not at all during the attempt. A faster heart rate in a tiny preterm baby may burn through the limited oxygen buffer more quickly, causing saturation levels to fall sooner. Meanwhile, the mechanism behind the reduced first-attempt success is less clear. It may reflect confounding by indication, since clinicians may reach for atropine in sicker, more fragile infants in whom intubation is intrinsically harder, or it may reflect a genuine drug-related effect that further research will need to disentangle.

The study arrives amid a growing body of evidence questioning routine atropine in neonates. A randomized clinical trial published in The Journal of Pediatrics in 2025 by Afifi, El-Naggar, Narvey and colleagues compared atropine with placebo for nonemergent neonatal intubation and found the drug offered no clear advantage, an accompanying commentary asking pointedly whether routine pre-intubation atropine does more harm than good. Earlier work in pediatric critical care, including studies by Jones and colleagues on more than three hundred critical care intubations, had likewise suggested that atropine’s effects on rhythm disturbances during intubation are more complicated than the simple reflex-blocking model implies, and that mortality benefits observed in some pediatric cohorts appeared unrelated to the drug’s influence on bradycardia.

For clinicians, the new findings do not amount to an immediate call to abandon atropine, but they do challenge the reflexive use of the drug in every neonatal intubation. The authors themselves conclude that the association between atropine and increased desaturation and lower first-attempt success warrants further study, and the observational design of the registry analysis means that unmeasured differences between patients who received the drug and those who did not could still influence the results. Randomized trials, such as the recent placebo-controlled study, will remain essential for establishing causation. In the meantime, the results give neonatologists something they have lacked: large-scale data suggesting that the most common cardiac premedication in the NICU may not prevent the worst outcome, and may carry costs of its own.

The broader significance of the study lies in what it says about how neonatal practice evolves. Many interventions in the NICU were adopted on physiological reasoning and small studies rather than rigorous outcome data, and the NEAR4NEOS registry has become a powerful instrument for auditing those practices across hundreds of thousands of recorded procedures. Previous reports from the same collaboration have shown that premedication with sedation and neuromuscular blockade is associated with fewer adverse events, that team stress correlates with complications, and that training level affects success rates. This latest analysis adds a crucial nuance to that picture, suggesting that the individual components of premedication regimens deserve scrutiny on their own terms. As the authors and their international collaborators continue to accumulate data, the question is shifting from whether atropine blunts a reflex, which it clearly does, to whether blunting that reflex, at the cost of faster desaturation and more attempts, actually serves the smallest patients best.

Subject of Research: Atropine use and adverse events during neonatal tracheal intubation

Article Title: Association of atropine use during neonatal intubation with cardiac arrest, severe bradycardia, and other adverse events: a report from NEAR4NEOS

Article References: Sawyer, T., Narvey, M., Tyler, M. D., Abou Mehrem, A., Iben, S., DeMartino, C., Tingay, D., Hodgson, K., Kim, J., Herrick, H., Unrau, J., Puia-Dumitrescu, M., Shay, R., DeMeo, S., Assaad, M.-A., O’Shea, J., Brajkovic, I., Quek, B. H., Glass, K., … DeMartino, C. (2026). Association of atropine use during neonatal intubation with cardiac arrest, severe bradycardia, and other adverse events: a report from NEAR4NEOS. Journal of Perinatology. https://doi.org/10.1038/s41372-026-02916-2

Image Credits: AI Generated

DOI: 10.1038/s41372-026-02916-2

Keywords: atropine, neonatal intubation, cardiac arrest, bradycardia, oxygen desaturation, NEAR4NEOS, premedication, neonatology, NICU, patient safety, Journal of Perinatology, registry study