The study, led by Jorge Luis Alvarado-Socarras together with Delia Edith Theurel-Martin and Edgar Fabián Manrique-Hernández, set out to answer a deceptively simple question: what happens when babies with prenatally predicted mild congenital diaphragmatic hernia are allowed to breathe spontaneously at birth, with intubation reserved only for those who deteriorate? The idea behind this so-called spontaneous breathing approach is not reckless. Advances in prenatal imaging now allow specialists to estimate, before delivery, how severe the lung compression is likely to be, using measures such as the lung-to-head ratio and the position of the liver. Babies whose findings fall into the mildest category might, in theory, manage without immediate mechanical ventilation, avoiding the potential harms of unnecessary tubes, sedation, and ventilator-induced lung injury.

To test what the existing literature actually supports, the team searched five major databases: PubMed/MEDLINE, Embase, Scopus, LILACS, and SciELO, covering the entire period from the inception of each database. The initial search was performed on November 27, 2024, and was subsequently updated through August 8, 2026. Two reviewers independently screened the records, a standard safeguard against selection bias, and the risk of bias in each included study was assessed according to its design. The certainty of the body of evidence was then graded using GRADE, the widely used framework that rates confidence in findings from high to very low. Because the available studies differed so much clinically and methodologically, the authors chose a narrative synthesis rather than pooling numbers into a single statistical estimate, a decision that reflects the fragmented nature of the evidence base.

What emerged from that search was strikingly thin. Only three observational studies qualified for inclusion, and together they described just 30 neonates who were initially managed with a spontaneous breathing approach rather than routine intubation. That is an extraordinarily small foundation for a question that touches the opening minutes of life for hundreds of babies each year. Observational studies, moreover, cannot randomize treatment; they simply report what happened in the centers that chose to try the gentler strategy, which means that selection of which babies received it may have been influenced by factors the studies did not fully capture.

The headline numbers from the review are sobering for advocates of selective intubation. Of the 30 neonates managed initially on spontaneous breathing, 16, or 53.3 percent, required unplanned intubation before surgery because of respiratory deterioration. The remaining 14 babies, 46.7 percent, avoided an unplanned pre-operative intubation and presumably proceeded toward surgical repair without the tube that guidelines would have placed at birth. In other words, in the pooled experience of these three studies, slightly more than half of the babies selected for the gentler approach ended up needing urgent intubation anyway, precisely the outcome the routine-intubation policy is designed to prevent or at least anticipate in a controlled manner.

On the question of survival, the picture is more encouraging but far from definitive. No deaths were reported in the included cohorts, which is a genuinely reassuring signal for a condition that remains one of the most challenging in neonatal intensive care. However, the authors flag an important caveat: in one of the studies, subgroup-specific survival to discharge could not be independently confirmed because the denominator reporting was incomplete. Without knowing exactly how many babies were in the spontaneous breathing subgroup, readers cannot verify what proportion survived. Adverse events and the use of extracorporeal membrane oxygenation, the heart-lung bypass technology reserved for the most severe cases, were uncommon across the included studies, but the authors are explicit that reporting limitations preclude definitive conclusions about safety or survival.

These nuances matter because the stakes of getting the decision wrong are asymmetric. A baby who is intubated unnecessarily may be exposed to complications of airway instrumentation and ventilation, but those risks are generally manageable in an experienced neonatal intensive care unit. A baby who is left breathing spontaneously and then deteriorates rapidly faces a race against time, with a compressed lung that may collapse further as swallowed air distends the herniated bowel. The physiological logic of immediate intubation is that it converts an unpredictable emergency into a controlled procedure performed by a prepared team, often in the delivery room, before the baby’s condition can spiral. The review’s finding that more than half of the selected babies deteriorated underscores how difficult it remains to predict, even with modern prenatal imaging, which newborns will truly tolerate spontaneous breathing.

The certainty assessment by GRADE delivers the review’s central verdict: the available evidence on spontaneous breathing in prenatally predicted mild congenital diaphragmatic hernia is of very low certainty and is insufficient to establish safety or effectiveness relative to routine intubation. Very low certainty means that the true effect could be substantially different from what these small observational studies suggest, and that any future evidence could easily change the conclusion. Three studies and 30 babies, drawn from centers that self-selected into trying the approach, simply cannot carry the weight of overturning a guideline that has protected newborns for generations. The authors are unambiguous in their conclusion: given the substantial heterogeneity and small sample sizes, routine intubation remains the standard of care.

That conclusion does not render the review pointless. On the contrary, it performs a valuable service by mapping the boundaries of current knowledge and exposing how little high-quality evidence underpins any attempt to individualize delivery-room management for this condition. The authors call for further prospective, standardized research before any clinical recommendation can be made, and the shape of that research is fairly clear from their analysis. A well-designed prospective study would need to define in advance which prenatal criteria qualify a baby as mild, standardize the criteria for rescue intubation, and follow outcomes with complete denominator reporting so that survival and complication rates can be calculated without ambiguity. Ideally, such work would be multicenter, because a condition as uncommon as congenital diaphragmatic hernia means that any single unit would need years to accumulate a meaningful number of patients.

For clinicians and expectant parents navigating a prenatal diagnosis today, the practical message is continuity rather than change. Prenatal imaging can identify babies likely to have mild disease, and that information is valuable for counseling, delivery planning, and ensuring that surgery and extracorporeal support are available if needed. But the delivery-room default should remain immediate endotracheal intubation, because the alternative has not been shown to be safe and, in the small published experience, led to urgent intubation in a majority of cases. The review also highlights a broader lesson for neonatology: practices that feel intuitively gentler, including non-invasive ventilation and spontaneous breathing strategies that have transformed care in other contexts such as preterm respiratory distress, cannot simply be transplanted to a condition with unique anatomy without rigorous testing. Until such testing is done, the tube goes in first, and the science of when it can safely wait remains an open question that the next generation of studies will need to answer.

Subject of Research: Non-routine intubation versus spontaneous breathing at birth in neonates with prenatally diagnosed mild congenital diaphragmatic hernia

Article Title: Non-routine intubation in prenatally diagnosed neonates with mild congenital diaphragmatic hernia: a systematic review

Article References: Alvarado-Socarras, J. L., Theurel-Martin, D. E., & Manrique-Hernández, E. F. (2026). Non-routine intubation in prenatally diagnosed neonates with mild congenital diaphragmatic hernia: a systematic review. BMC Pediatrics. https://doi.org/10.1186/s12887-026-07800-8

Image Credits: AI Generated

DOI: 10.1186/s12887-026-07800-8

Keywords: congenital diaphragmatic hernia, prenatal diagnosis, neonatal intubation, spontaneous breathing approach, systematic review, neonatology, ventilation, non-invasive ventilation, GRADE certainty of evidence, neonatal outcomes, delivery room stabilization, BMC Pediatrics

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