What makes these numbers remarkable is not only their magnitude but their consistency. Survival statistics for infants at the very edge of viability vary enormously between countries, and even between hospitals within the same country, because they depend on a tangled web of decisions: whether obstetricians transfer mothers before delivery, whether resuscitation is attempted at all, and how intensively each fragile organ system is managed afterward. The Japanese review addresses this complexity directly, linking outcomes not just to clinical technique but to the architecture of the healthcare system itself. Three structural pillars emerge from the analysis: regionalized perinatal care that promotes antenatal maternal transfer, a nationwide clinical network that benchmarks every participating center, and universal health insurance that removes financial barriers to intensive care.

The first pillar, regionalization, is deceptively simple. Rather than allowing extremely preterm labor to be managed wherever it happens to occur, Japan’s perinatal system encourages the transfer of the pregnant woman, not the newborn, to a facility equipped with the highest level of neonatal intensive care. This means the infant is born in the very place where ventilators, surfactant, specialized nursing and round-the-clock physician coverage already exist. Epidemiologic studies cited in the review show that outborn infants, those born outside tertiary centers and transported after delivery, fare substantially worse than inborn infants, a finding that transforms maternal transfer from a logistical preference into a life-saving intervention. The review also notes distinctive Japanese delivery practices, including cesarean delivery en caul, in which the infant is delivered still encased within the intact amniotic sac, a technique designed to protect the fragile head and umbilical cord during extraction and to allow a gentler transition to extrauterine life.

The second pillar is data. Since the establishment of the Neonatal Research Network of Japan, virtually every very low birth weight infant admitted to a participating neonatal intensive care unit has been entered into a central database, creating a continuous national audit of survival and morbidity. This infrastructure allows centers to compare their outcomes against national benchmarks, identify drift, and refine protocols in response to evidence rather than anecdote. The review emphasizes that this data-driven quality improvement cycle, in which outcomes are monitored continuously and fed back into clinical practice, is not an optional extra but a core mechanism sustaining Japan’s results. International comparisons conducted through networks such as the International Network for Evaluating Outcomes of very low birth weight, very preterm neonates have repeatedly shown that Japan’s survival figures at 22 and 23 weeks exceed those of the United States, Sweden and other high-income countries, while rates of severe intraventricular hemorrhage and necrotizing enterocolitis remain comparatively low.

The third pillar, universal health insurance, is often overlooked in discussions of neonatal outcomes, yet it underpins everything else. In Japan, the cost of prolonged intensive care, which can stretch across months and consume enormous resources, is not borne by individual families in ways that might pressure clinicians toward less aggressive management. The review suggests that this financial context supports a culture in which active resuscitation at 22 and 23 weeks is the default rather than the exception, and in which treatment decisions are framed primarily around physiology and prognosis rather than around cost.

Clinical practice itself, the review argues, is characterized by meticulous, individualized, pathophysiology-based management. This begins at the moment of birth with active resuscitation, including invasive respiratory support. Unlike centers in some countries that favor early non-invasive strategies such as continuous positive airway pressure, Japanese practice at these gestational ages frequently proceeds directly to intubation and mechanical ventilation, on the reasoning that the lungs of a 22-week infant, with surfactant deficiency and structural immaturity, cannot generate the transpulmonary pressures needed for gas exchange without direct support. The review situates this within international evidence, noting that while non-invasive ventilation strategies have been associated with reduced bronchopulmonary dysplasia in broader preterm populations, their application at the very limits of viability remains contested, and that Japanese centers have chosen invasive support as a deliberate strategy tailored to this extreme population.

Perhaps the most distinctive element of Japanese neonatal practice described in the review is echocardiography-guided hemodynamic management. Rather than treating blood pressure numbers in isolation, Japanese clinicians use functional echocardiography to assess cardiac output, ductal shunting, and ventricular performance, allowing targeted intervention for conditions such as patent ductus arteriosus and late-onset circulatory collapse. The review describes how routine echocardiography enables proactive diagnosis and tailor-made treatment of the ductus arteriosus, a vessel that in preterm infants often fails to close after birth and can steal blood from the systemic circulation, compromising perfusion of the brain, gut and kidneys. Japanese practice has historically favored active treatment of hemodynamically significant ductal shunting, in contrast to the expectant management approach that has gained ground in some Western centers. The review acknowledges that the effectiveness of these practices remains uncertain and that ongoing randomized trials, including recent studies comparing early treatment with expectant management of the ductus, will be essential to clarify which approach truly benefits infants at these gestational ages.

Neuroprotection receives equally intensive attention. The germinal matrix, the highly vascular region lining the ventricles of the premature brain, is exquisitely vulnerable to fluctuations in cerebral blood flow and pressure, and severe intraventricular hemorrhage remains one of the most devastating complications of extreme prematurity. Japanese management emphasizes stabilization of hemodynamics from the first minutes of life, careful control of carbon dioxide levels during ventilation, avoidance of excessive fluid administration, and meticulous handling to minimize stress responses. The review also describes the use of inhaled nitric oxide for persistent pulmonary hypertension of the newborn, standardized across Japanese centers even at extremely early gestational ages, and the recognition of late-onset circulatory collapse, a syndrome of adrenal insufficiency and hypotension appearing days to weeks after birth, as a distinct entity requiring targeted steroid therapy. Sedation and analgesia practices are also being reconsidered, with national surveys examining how best to balance stress relief against the hypotensive effects of opioids in ventilated infants.

Specialized nursing care forms the final layer of this package. The review highlights the role of Japanese neonatal nursing, with its historic emphasis on individualized developmental care, precise positioning using low-volatile organic compound polyurethane foam devices, and continuous observation of subtle clinical changes. Nurses in Japanese neonatal intensive care units are trained to detect early signs of deterioration, manage the delicate balance between handling necessary for treatment and the stress that handling imposes, and support families through what is often a months-long journey. This nursing infrastructure, the review suggests, is inseparable from the medical interventions, because the survival of an infant weighing 400 grams depends as much on the precision of daily care as on the sophistication of ventilator settings.

The review is careful to temper enthusiasm with caution. It notes that while survival has improved, neurodevelopmental outcomes at 2 to 3 years of corrected age remain a critical measure, and that the effectiveness of many individual practices, from echocardiography-guided circulatory management to specific neuroprotective strategies, has not been established through rigorous trials. The authors argue that what matters may not be any single intervention but the integration of multiple practices into a coherent package of care, delivered within a system that monitors outcomes continuously and refines strategies in response to evidence. For clinicians and policymakers worldwide grappling with how to approach infants born at the very edge of viability, the Japanese experience offers a compelling, if not yet fully proven, template: regionalize care, benchmark relentlessly, remove financial barriers, and treat each infant not as a statistical category but as a physiological individual whose fragile organ systems demand pathophysiology-based, individualized management from the first breath onward.

Subject of Research: Neonatal outcomes and care practices for infants born at 22-23 weeks' gestation in Japan

Article Title: Japan at the limits of viability: national experience and evolving outcomes of infants born at 22–23 weeks’ gestation

Article References: Isayama, T., Nakanishi, H., Konishi, M., Kokubo, M., Fujimura, M., Hirano, S., & Kusuda, S. (2026). Japan at the limits of viability: national experience and evolving outcomes of infants born at 22–23 weeks’ gestation. Pediatric Research. https://doi.org/10.1038/s41390-026-05266-z

Image Credits: AI Generated

DOI: 10.1038/s41390-026-05266-z

Keywords: extreme prematurity, limits of viability, neonatal intensive care, Japan, 22 weeks gestation, 23 weeks gestation, survival rates, intraventricular hemorrhage, patent ductus arteriosus, echocardiography, neuroprotection, Neonatal Research Network of Japan

Milrinone is a pharmacological tool with a distinctive mechanism. Unlike classic vasopressors, which squeeze blood vessels to raise blood pressure, milrinone works by inhibiting an enzyme called phosphodiesterase type 3, or PDE3. This inhibition prevents the breakdown of cyclic AMP, a key intracellular signaling molecule, inside heart muscle cells and vascular smooth muscle. The result is a dual action: the heart contracts more forcefully and relaxes more efficiently between beats, while blood vessels dilate, lowering the resistance against which the heart must pump. In theory, this combination makes milrinone ideal for newborns struggling with acute pulmonary hypertension or with the hemodynamic turbulence that can follow the closure of a patent ductus arteriosus, a fetal blood vessel that sometimes fails to seal after birth. In practice, however, the vasodilating effect that makes the drug attractive can also tip a fragile infant into systemic hypotension—a drop in blood pressure severe enough to threaten blood flow to the brain, kidneys, and gut.

That concern is precisely what motivated the Iowa team, led by neonatologist Trassanee Chatmethakul together with Adrianne Bischoff, Danielle Rios, and Patrick McNamara, to take a closer look. Recent years have seen a marked increase in milrinone use for preterm infants, yet safety data in the extremely low gestational age population remain strikingly thin. Uncontrolled clinical reports had suggested a link between the drug and hypotension, while a small randomized trial using loading doses found tachycardia—abnormally fast heart rate—but no significant blood pressure drop. Animal studies added another layer of uncertainty, hinting that the newborn myocardium, particularly in the early transitional period just after birth, may be relatively unresponsive to the inotropic, or contractility-boosting, effects of PDE3 inhibition. In other words, the very population in which milrinone is increasingly deployed may be the one in which its risks are least understood.

To fill that gap, the researchers conducted a retrospective cohort study at the University of Iowa’s level IV Neonatal Intensive Care Unit, examining the medical records of infants born between 2018 and 2020. They included newborns delivered at a gestational age of 22 weeks and zero days through 28 weeks and six days who received milrinone during the first four postnatal weeks. Crucially, they excluded infants who were already hypotensive when milrinone was started, as well as those with known or suspected genetic syndromes or major congenital malformations, ensuring that the analysis focused on babies whose blood pressure changes could reasonably be linked to the drug exposure itself. The study was approved by the university’s Institutional Review Board, and the team gathered demographic and clinical data from electronic medical records.

The primary outcome was carefully defined: the presence of hypotension lasting at least one hour within the first six hours after the milrinone infusion began. Hypotension was defined either as a diastolic pressure, or both diastolic and mean arterial pressure, falling below the third percentile for gestational age at the time of exposure, or as the need to start or escalate another vasoactive medication. Secondary outcomes included changes in the respiratory severity score—a composite measure of ventilator support and oxygen requirements—the need for new vasopressors, the vasoactive-inotropic score, and a range of neonatal morbidities following exposure.

The cohort comprised 34 extremely low gestational age infants, with a mean gestational age of 24.5 weeks and a mean birth weight of just 676 grams. Of these, eight infants—23.5 percent—developed hypotension or required escalation of vasoactive therapy within the monitoring window. That figure is the study’s central alarm bell. Nearly one in four of these vulnerable newborns experienced a clinically significant blood pressure decline in the hours after milrinone was started, a rate the authors describe as concerning, particularly given that the drug is often administered precisely to stabilize circulation.

What makes the study especially valuable is its identification of who was most at risk. The infants who became hypotensive were, at the time milrinone was initiated, younger and smaller than their counterparts who tolerated the drug well. Their postmenstrual age—the gestational age plus the time since birth—averaged 27.3 weeks compared with 28.8 weeks in the non-hypotensive group, a difference that reached statistical significance. They also weighed less, averaging 796 grams versus 1104 grams. Perhaps most tellingly, the hypotensive infants had a higher respiratory severity score during the first four hours of milrinone exposure, 7.6 versus 4.4, indicating that they were sicker from a respiratory standpoint and required more intensive ventilatory and oxygen support. Taken together, these findings suggest that lower postnatal age, lower weight, and poorer respiratory status all mark infants at heightened risk of a blood pressure crash after milrinone.

The authors are careful to acknowledge the interpretive limits of their data. The hypotension they observed could be a direct pharmacological effect of milrinone’s vasodilating action, or it could reflect the natural course of sicker infants whose underlying pathophysiology—sepsis, pulmonary hypertension, ductal steal, or immature myocardial function—was already driving them toward cardiovascular collapse. With only 34 infants in the cohort, the dataset was too small to disentangle the statistical effect of polypharmacy, the simultaneous use of multiple vasoactive and supportive medications that is routine in this population. Retrospective design adds further constraints: the researchers could observe associations, but not prove causation, and treatment decisions were made by clinicians rather than randomized by protocol.

Even so, the study’s implications for clinical practice are concrete. The findings underscore the importance of close hemodynamic monitoring in the hours immediately following milrinone initiation, particularly for the smallest, youngest, and most respiratory-compromised infants. They also support a philosophy of physiology-based, targeted utilization of milrinone—reserving the drug for infants whose specific pathophysiology genuinely calls for PDE3 inhibition, rather than administering it broadly as a general circulatory tonic. This approach, championed in neonatal hemodynamics literature by McNamara and colleagues, emphasizes matching cardiovascular support to the underlying disease mechanism instead of applying one-size-fits-all protocols.

The broader context makes this work timely. Milrinone’s mechanism—enhancing contractility while reducing afterload—remains uniquely suited to conditions such as pulmonary hypertension of the newborn and the post-closure hemodynamic shifts that increasingly accompany modern PDA treatment. As more extremely preterm infants survive to receive these interventions, the demand for precise safety data will only grow. The Iowa team’s study, though small, provides a crucial first map of the risk landscape: the youngest, lightest, and most ventilator-dependent infants are the ones whose blood pressures deserve the closest watch when milrinone is started. Larger, prospective studies are now warranted to define the drug’s full safety profile and to establish optimal dosing and monitoring parameters for the most fragile patients in the nursery. Until then, the message to neonatal intensivists is clear—milrinone can be a lifeline, but in the tiniest newborns it must be deployed with vigilance, and with a blood pressure cuff never far away.

Subject of Research: Milrinone-associated systemic hypotension risk in extremely low gestational age newborns

Article Title: Characteristics of extremely low gestational age newborns receiving milrinone and possible risk factors associated with the development of systemic hypotension

Article References: Chatmethakul, T., Bischoff, A. R., Rios, D. R., & McNamara, P. J. (2026). Characteristics of extremely low gestational age newborns receiving milrinone and possible risk factors associated with the development of systemic hypotension. Journal of Perinatology. https://doi.org/10.1038/s41372-026-02773-z

Image Credits: AI Generated

DOI: 10.1038/s41372-026-02773-z

Keywords: milrinone, extremely preterm infants, neonatal hypotension, neonatal intensive care, phosphodiesterase inhibitor, patent ductus arteriosus, pulmonary hypertension, hemodynamic monitoring, respiratory severity score, vasoactive medications, retrospective cohort study, neonatal hemodynamics

The ductus arteriosus is a normal feature of fetal circulation, a short muscular vessel that shunts blood away from the lungs while the baby is still in the womb and oxygen comes from the placenta. In most newborns, the vessel closes within hours or days of birth. In babies born before 32 weeks of gestation, however, closure often fails or is delayed. The resulting patent ductus arteriosus, or PDA, creates a left-to-right shunt: oxygenated blood leaving the heart is diverted back toward the lungs, increasing pulmonary blood flow and pressure. When that shunt becomes hemodynamically significant, meaning it is large enough to disturb circulatory function, the flooded, immature lung capillaries are thought to become vulnerable to rupture, particularly in lungs already injured by prematurity and mechanical ventilation.

The research team, led by Li Yang and colleagues in the Department of Neonatology at Guangyuan Central Hospital in Sichuan, China, set out to quantify this relationship. They reviewed the records of 482 very preterm infants, all born at less than 32 weeks of gestation, who were admitted to their neonatal intensive care unit between January 2019 and October 2025. Because the study was retrospective, the investigators worked backward from outcomes that had already occurred, using univariate and multivariate logistic regression to separate factors genuinely associated with pulmonary hemorrhage from those that merely appeared linked because of confounding. For infants diagnosed with a patent ductus arteriosus, the team calculated the Patent Ductus Arteriosus Severity Score, a composite measure that grades the clinical and hemodynamic weight of the defect.

The headline finding is stark. Of the 482 infants in the cohort, 93, or 19.3 percent, developed neonatal pulmonary hemorrhage. Among those who bled, 42 died before discharge, a post-hemorrhage mortality rate of 45.2 percent. Those numbers underline why the condition commands such dread in neonatology: nearly one in five very preterm infants in this cohort experienced a lung hemorrhage, and nearly half of the affected babies did not survive it. Preventing even a fraction of these events, or identifying them earlier, could translate into a meaningful survival gain for this population.

When the researchers ran their multivariate analysis across the entire cohort, five factors remained independently associated with pulmonary hemorrhage: lower gestational age, lower birth weight, a lower five-minute Apgar score, premature rupture of membranes, and hemodynamically significant PDA. Each of these tells a clinically coherent story. Earlier gestational age and lower birth weight reflect pulmonary immaturity and fragile capillary networks. A depressed five-minute Apgar score signals birth depression and possible hypoxic stress on vascular integrity. Premature rupture of membranes is associated with intrauterine inflammation and infection, which can precondition the fetal lung for injury. And hemodynamically significant PDA supplies the mechanical mechanism, the excessive pulmonary blood flow, that pushes those weakened capillaries over the edge.

To make these findings more usable at the bedside, the team built nomograms, graphical scoring tools that allow clinicians to total up a patient’s individual risk factors and read off an estimated probability of the outcome. They internally validated these tools using the bootstrap method, a resampling technique that estimates how much a model’s apparent performance is inflated by overfitting to the original dataset. In the subgroup of infants with PDA, the nomogram for predicting pulmonary hemorrhage achieved an area under the receiver operating characteristic curve, or AUC, of 0.858, with a 95 percent confidence interval of 0.812 to 0.904. After bootstrap correction, the value settled at 0.837, still comfortably in the range considered good discrimination for a clinical prediction tool.

One of the more contemporary aspects of the study is its use of SHAP analysis, short for SHapley additive explanations, a machine learning interpretation method borrowed from game theory that quantifies how much each individual predictor contributes to a model’s output. Applied here, SHAP revealed that gestational age contributed most to the risk assessment of pulmonary hemorrhage, followed by hemodynamically significant PDA and then birth weight. In practical terms, this means the single strongest signal of danger remains how early the baby was born, but the severity of the ductal shunt carries weight nearly comparable to birth weight. The approach gives clinicians an intuitive visualization of why the model flags a particular infant, addressing a common criticism that statistical prediction tools operate as unexplained black boxes.

The second half of the analysis focused on the sickest subgroup: the 81 infants who had both a patent ductus arteriosus and a pulmonary hemorrhage. Here the question shifted from who bleeds to who dies after bleeding. In multivariate analysis, a higher Patent Ductus Arteriosus Severity Score was independently associated with in-hospital mortality, with an odds ratio of 3.614 and a 95 percent confidence interval of 1.918 to 6.812. In plain language, each step up in severity score roughly tripled or more the odds of dying, a strong and statistically robust association whose confidence interval lies well above the null. This suggests the score, which aggregates indicators of ductal hemodynamic burden, may function as an early warning marker for the babies least likely to survive a hemorrhagic event.

The clinical implications are considerable. If hemodynamically significant PDA is independently linked to pulmonary hemorrhage, then the intensity of monitoring and treatment of the ductus in very preterm infants, whether through fluid restriction, pharmacologic closure, or other strategies, may matter not only for classic ductal outcomes but for lung bleeding itself. Meanwhile, the severity score’s association with mortality offers a way to stratify infants with PDA who do hemorrhage, helping clinicians and families calibrate expectations and direct intensive resources toward those at highest risk. The nomograms, once validated, could become routine bedside calculators in neonatal units caring for extremely premature babies.

The authors themselves are careful about the limits of what they can claim. As a single-center retrospective cohort, the study cannot establish that treating the ductus prevents hemorrhage; association is not causation, and unmeasured variables may still influence both conditions. The internal bootstrap validation, while methodologically sound, does not substitute for external validation in larger, independent cohorts, which the researchers explicitly identify as the necessary next step before the tools enter routine practice. Still, by combining a large consecutive cohort, adjusted regression modeling, machine learning interpretability, and validated risk scores, the study offers one of the clearest quantitative portraits to date of how a simple failure of fetal circulation to close can help push a preterm lung into its most dangerous complication, and how a structured score may tell clinicians, early, which of these babies are in the gravest danger.

Subject of Research: Association between patent ductus arteriosus and neonatal pulmonary hemorrhage and mortality in very preterm infants

Article Title: Association of patent ductus arteriosus and severity score with neonatal pulmonary hemorrhage and mortality in very preterm infants: a retrospective cohort study

Article References: Yang, L., Han, X., Xu, X., Bai, L., Li, Y., Zhao, Z., & Duan, Y. (2026). Association of patent ductus arteriosus and severity score with neonatal pulmonary hemorrhage and mortality in very preterm infants: a retrospective cohort study. BMC Pediatrics. https://doi.org/10.1186/s12887-026-07663-z

Image Credits: AI Generated

DOI: 10.1186/s12887-026-07663-z

Keywords: patent ductus arteriosus, very preterm infants, neonatal pulmonary hemorrhage, PDA severity score, mortality, nomogram, SHAP analysis, logistic regression, neonatology, risk factors, retrospective cohort study, BMC Pediatrics

The study, published in the Journal of Perinatology by a team led by Sharada H. Gowda of Indiana University and Riley Children’s Hospital, gathered written PDA management guidelines from hospitals belonging to the Children’s Hospitals Neonatal Consortium, a network of 44 quaternary-level neonatal intensive care units in the United States and Canada. Between November 2023 and February 2024, the researchers emailed designated representatives at every member center, asking whether their institution maintained a formal written guideline for managing the condition in premature infants and requesting a copy if one existed. Thirty-eight of the 44 centers responded, an 86 percent response rate, and 25 of those, roughly two-thirds, provided written protocols for analysis.

What the researchers found was a field united by a broad philosophy but divided on nearly every practical detail. Most guidelines described a stepwise approach that begins with expectant, or watchful, management, escalates to drug therapy when the ductus becomes hemodynamically significant, and reserves procedural closure for infants who fail medical treatment. Yet beneath that shared skeleton, the specifics varied dramatically. Screening strategies, diagnostic thresholds, drug choices, dosing schedules, feeding policies, and the timing of interventions all differed from center to center, sometimes in striking ways.

The diagnosis itself is the first fault line. Hemodynamically significant PDA, abbreviated hsPDA, refers to a ductal shunt substantial enough to disturb the infant’s circulation, potentially stealing blood from the gut and lungs and contributing to serious complications such as bronchopulmonary dysplasia, necrotizing enterocolitis, intraventricular hemorrhage, and prolonged intensive care stays. Because clinical signs such as a heart murmur, bounding pulses, or worsening respiratory status are notoriously nonspecific, objective echocardiographic assessment has become the cornerstone of diagnosis. In the survey, 88 percent of guidelines specified echocardiographic criteria, most commonly ductal diameter, the left atrium-to-aorta ratio, shortened isovolumic relaxation time, and flow reversal in the descending aorta. Less frequently cited markers included flow reversal in the celiac trunk or middle cerebral artery, parameters that reflect more severe systemic hypoperfusion.

Clinical criteria appeared in 80 percent of the guidelines, and respiratory support requirements dominated that category. Among centers that referenced breathing support, 42 percent cited escalating respiratory needs, 37 percent required at least noninvasive ventilation or nasal continuous positive airway pressure, and a small number demanded intubation or used a quantitative respiratory severity score. Other clinical triggers included pulmonary edema, cardiomegaly, pulmonary hemorrhage, widened pulse pressure, and a hyperdynamic precordium, the pounding chest sensation produced by a large shunt. Only 12 percent of centers, however, employed a formal clinical scoring system, a strikingly low figure given growing evidence that composite scores may predict outcomes better than any single parameter.

Screening practices revealed similar heterogeneity. Ninety-two percent of guidelines described risk-based or symptom-based screening for the condition, but the timing of the first echocardiogram ranged from within 36 hours of birth for the most immature infants at some centers to delayed evaluation in the second week of life at others. Some centers screened purely on gestational age, some purely on symptoms, and about a third used a combination of the two. This scatter mirrors the unsettled evidence base: randomized trials and meta-analyses have repeatedly failed to show a clear benefit of routine early treatment compared with expectant management, leaving each institution to chart its own course through the ambiguity.

When treatment is warranted, ibuprofen has emerged as the workhorse drug, recommended as first-line pharmacotherapy by more centers than any alternative. Indomethacin, the traditional cyclooxygenase inhibitor that dominated PDA therapy for decades, has been displaced, while intravenous acetaminophen, increasingly popular at the bedside, remains underrepresented in formal protocols, a discrepancy the authors interpret as evidence that written guidelines lag behind evolving clinician preferences. A quarter of centers recommended prophylactic therapy for the highest-risk infants, such as those born before 25 to 26 weeks without antenatal steroid exposure, with some using indomethacin and others administering acetaminophen at 15 milligrams per kilogram every six hours for twelve doses. The number of treatment courses allowed also varied widely, from a single course at one center to as many as four at others.

Feeding practices during therapy, long a source of anxiety because of theoretical concerns about gut injury, showed a reassuring convergence. Not a single guideline recommended holding feeds entirely during pharmacotherapy, and most centers either allowed full feeding, restricted volume modestly, or permitted trophic feeds. This aligns with accumulating evidence that withholding feeds prolongs the time needed to reach full nutrition without reducing gastrointestinal complications, and that feed interruption may even explain some of the poor outcomes previously attributed to the drugs themselves. On the expectant side, centers that described conservative management uniformly recommended fluid restriction of 120 to 140 milliliters per kilogram per day, with most also endorsing higher breathing pressures, diuretics, and higher hemoglobin targets, while explicitly encouraging rather than restricting nutrition.

Perhaps the most consequential trend captured by the survey is the rise of transcatheter closure. Ninety-two percent of guidelines addressed device-based closure, and 83 percent of those recommended a course of pharmacotherapy before resorting to the catheter procedure. Minimum weight thresholds for device closure ranged from 650 to 1,800 grams, and several centers specified waiting until 14 or 21 days of life. Surgical ligation, once the default definitive treatment, appeared in only 48 percent of guidelines and was frequently reserved for infants too small for the catheter approach. The shift reflects the maturation of minimally invasive occluder devices and a growing recognition that surgical ligation carries risks of its own, including vocal cord paralysis and the controversial post-ligation syndrome, for which, remarkably, only one center in the entire consortium offered written guidance.

The authors are careful to note the study’s limits: written guidelines may not match what actually happens at the bedside, the survey captured no patient outcomes, and the findings come exclusively from large referral centers that may not represent community hospitals. The timing also matters, since the data collection preceded several landmark trials, including BeNeDuctus, BabyOSCAR, and the Neonatal Research Network PDA Randomized Clinical Trial, each of which concluded that conservative management performs as well as or better than drug treatment, though all were constrained by early termination, treatment crossover, and the exclusion of the sickest infants. Still, the picture that emerges is of a specialty in transition, holding onto a common stepwise framework while awaiting the evidence needed to settle its deepest disagreements. For the smallest patients, whose lives often hinge on decisions made within hours of birth, the path from a leaking vessel in the heart to a healed one still depends, to a remarkable degree, on which hospital door they enter first.

Subject of Research: Variation in diagnosis and management of hemodynamically significant patent ductus arteriosus across neonatal intensive care units

Article Title: Variations in diagnosis and management of hemodynamically significant patent ductus arteriosus across neonatal intensive care units in the Children’s Hospitals Neonatal Consortium

Article References: Gowda, S. H., Levy, P. T., Hamrick, S., Keene, S., Sen, S., Rajgarhia, A., Rao, R., Ball, M. K., Weems, M. F., & on behalf of CHNC Cardiac Focus Group (2026). Variations in diagnosis and management of hemodynamically significant patent ductus arteriosus across neonatal intensive care units in the Children’s Hospitals Neonatal Consortium. Journal of Perinatology. https://doi.org/10.1038/s41372-026-02910-8

Image Credits: AI Generated

DOI: 10.1038/s41372-026-02910-8

Keywords: patent ductus arteriosus, preterm infants, neonatal intensive care, echocardiography, ibuprofen, acetaminophen, transcatheter closure, surgical ligation, clinical guidelines, Children's Hospitals Neonatal Consortium, hsPDA, neonatology

The ductus arteriosus is a fetal shortcut that connects the pulmonary artery to the aorta, allowing blood to bypass the fluid-filled, non-functioning lungs before birth. In most babies, the vessel seals itself within the first days of life. In premature infants, however, closure often fails. The problem is remarkably common: an estimated 66 to 79 percent of neonates born weighing less than 1000 grams still have a patent ductus at seven days of age. Whether that open vessel is merely a lingering remnant or a genuine threat to fragile organs depends on its hemodynamic significance, meaning the degree to which it steals blood from the systemic circulation and floods the lungs. And that, precisely, is where consensus collapses, because no universally accepted standard exists for defining when a ductus has crossed the line from benign to dangerous.

The new study, led by Paige E. Condit and John S. Hokanson of the University of Wisconsin-Madison, set out to map this contested terrain. Between February and April 2024, the researchers distributed an anonymous Qualtrics survey to members of the American Academy of Pediatrics Section on Neonatal-Perinatal Medicine, the Section on Cardiology and Cardiac Surgery, and the Pediheart.net online community. Roughly 504 providers began the survey and 422 completed it, yielding an overall response rate of about 8 percent. The analytic sample included 315 neonatologists and 107 pediatric cardiologists. Importantly, the neonatology group was stratified by whether the respondent’s institution offered in-house catheter-based ductal closure, a proxy for the highest-acuity Level IV neonatal intensive care units, allowing the investigators to probe whether access to advanced procedural capability shapes clinical judgment.

The headline result is a portrait of deep disagreement over echocardiography, the ultrasound technique on which virtually all modern ductal assessment rests. Respondents were asked to rank the clinical utility of 14 echocardiographic parameters on a three-point importance scale; the analysis focused on the nine parameters most commonly included in published scores and guidelines. Of those nine, the specialists agreed on the importance of only two: retrograde flow in the post-ductal aorta and the diameter of the ductus itself. For the remaining seven, including measures of left ventricular output, left atrial to aortic root ratio, and end-diastolic flow velocity in the branch pulmonary arteries, neonatologists and cardiologists assigned statistically different levels of both familiarity and importance. The largest familiarity gaps appeared for pulmonary artery end-diastolic flow velocity and left ventricular outflow, with effect sizes reaching the large range, a signal that the two specialties are not merely quibbling over fine points but diverging on fundamental diagnostic building blocks.

One intriguing pattern emerged from the stratification: neonatologists working at centers with in-house catheter closure capability tended to answer more like cardiologists than did their colleagues at centers without such programs. The authors attribute this to daily collaboration, noting that proximity to interventional cardiology likely exposes neonatologists to the same imaging vocabulary and interpretive habits. The implication is sobering for the field, because it suggests that even within a single specialty, the perceived meaning of an echocardiographic image may depend less on the image itself than on the institutional culture surrounding it. When two subspecialties disagree on which markers define hemodynamic significance, confusion can ripple through clinical handoffs, treatment decisions, and even the design of research studies, since cardiology-led and neonatology-led investigations may prioritize different aspects of ductal evaluation.

Formal scoring systems, which were developed precisely to resolve this ambiguity, remain strikingly underused. Only a minority of respondents reported employing any echocardiographic or clinical scoring system, with routine use ranging from 7.8 percent among neonatologists without catheter programs to 19.4 percent among those with them. The survey was conducted before the American Academy of Pediatrics released its recent clinical practice guideline, which recommends a combined echocardiographic and clinical approach with specific criteria required from each domain, so adoption may shift. But the authors point to a deeper problem: several validated scores exist, including the El-Khuffash score, which incorporates gestational age, ductal diameter, flow velocity, and left ventricular measures and has shown strong prediction of chronic lung disease or death with an area under the curve of 0.92, yet none has been proven in a randomized trial to improve outcomes when used to guide treatment compared with clinical judgment alone. A small feasibility trial of score-guided therapy did not demonstrate a statistically significant benefit, and the Iowa score’s reported reductions in severe bronchopulmonary dysplasia cannot be cleanly attributed to the score because the protocol bundled early screening echocardiography and other care changes together.

The survey also documented a quiet revolution in treatment delivery. Medical therapy was available to 99 percent of respondents, but prophylactic treatment was rare, reported by just 12.3 percent. Among first-line agents, acetaminophen narrowly led at 32.8 percent, followed by ibuprofen at 30.5 percent and the older indomethacin at 23.9 percent, with significant differences between specialties, partly because nearly half of cardiologists reported not making these pharmacologic recommendations at all. Most providers, 59 percent, said they would attempt medication-based closure twice before recommending a procedure, while about a quarter would try three times. When it came to procedural closure, the landscape has flipped: 72.1 percent of respondents said they rarely recommend surgical ligation, while catheter-based occlusion, recommended often by 65.1 percent of cardiologists and 48.1 percent of catheter-equipped neonatologists, has been rapidly adopted. An overwhelming 89 percent of respondents named the Amplatzer Piccolo device as their preferred occlusion device, a preference that did not differ by specialty. This shift follows studies suggesting better respiratory outcomes and lower mortality with transcatheter closure compared with surgery, even though no definitive trial has yet shown transcatheter closure to be superior to expectant management.

Screening practices added another layer of variation. Only 13.5 percent of respondents reported that their facility used routine screening echocardiograms for ductal evaluation. Among those who did, the average timing was 28.3 weeks’ gestation, but the spread was wide: neonatologists with in-house catheter programs screened earliest at a mean of 27.5 weeks, those without screened at 27.8 weeks, and cardiologists reported a mean of 31.0 weeks, a statistically significant difference with a medium effect size. The authors caution, however, that the question about screening echocardiography may have been interpreted differently across specialties, a reminder that survey-based comparisons of practice carry their own measurement hazards.

Indeed, the study’s limitations deserve as much attention as its findings. With an 8 percent response rate, non-response bias is a real concern; respondents may be more interested or experienced in ductal management than their silent colleagues, so the results reflect an engaged subset rather than a nationally representative sample. The survey did not capture practice setting, patient volume, or how often respondents actually manage hsPDA, all of which could confound the specialty comparisons. Membership overlap between the cardiology organizations means some cardiologists may have received duplicate invitations and potentially responded more than once, and multiple responses from the same institution could have skewed resource-availability estimates. The survey instrument lacked formal psychometric validation, multiple statistical comparisons were performed without correction for multiplicity, and respondents averaged 18 years in practice, which may not capture the habits of newer generations of clinicians.

Still, the big picture is hard to escape. A vessel present in most extremely premature infants is being diagnosed, scored, medicated, and closed in wildly different ways across the country, by specialists who cannot agree on which ultrasound measurements matter most. The authors call for studies that correlate echocardiographic findings with clinical outcomes and with hemodynamic data from cardiac catheterization, the gold standard of direct measurement, to finally anchor the definition of hemodynamic significance in physiology rather than tradition. Until that evidence arrives, the treatment of the premature ductus will remain what this survey reveals it to be: a high-stakes judgment call, made at the bedside of the smallest patients, under rules that two specialties are still writing separately.

Subject of Research: Diagnosis and management of hemodynamically significant patent ductus arteriosus in premature infants

Article Title: Current practices in the management of hemodynamically significant patent ductus arteriosus

Article References: Condit, P. E., Erdmann, A. A., Zhang, X., Ndukwe, E., Fernandez, J., & Hokanson, J. S. (2026). Current practices in the management of hemodynamically significant patent ductus arteriosus. Journal of Perinatology. https://doi.org/10.1038/s41372-026-02914-4

Image Credits: AI Generated

DOI: 10.1038/s41372-026-02914-4

Keywords: patent ductus arteriosus, premature infants, echocardiography, neonatology, pediatric cardiology, catheter closure, scoring systems, survey, neonatal intensive care, acetaminophen, ibuprofen, surgical ligation

Pulmonary agenesis is among the rarest congenital malformations of the respiratory system. It arises when the lung bud, the embryonic outgrowth of the foregut that normally branches into the airways and lung parenchyma, fails to develop on one side. The result is a complete absence of the affected lung tissue, airway, and vascular supply, rather than an underdeveloped lung that is merely small. The condition can affect either lung, and its reported incidence varies widely across older case series, in part because many affected infants die before a diagnosis is ever made. When one lung is missing, the remaining lung must carry the entire burden of gas exchange, and the cardiovascular system must adapt to a shifted distribution of blood flow. Survival is possible, particularly with unilateral agenesis and no other major anomalies, but the condition is frequently complicated by recurrent infections and, as in this case, pulmonary vascular disease.

The clinical course of the infant described in the report illustrates why the diagnosis is so often delayed. Shortly after birth she developed severe respiratory distress, a presentation that in a neonate is far more commonly explained by pneumonia, sepsis, transient tachypnea, or aspiration than by a missing lung. At the first facility she encountered, clinicians treated her for presumed pneumonia. When she failed to improve, she was referred onward to Tikur Anbessa Specialized Hospital, the tertiary referral center affiliated with Addis Ababa University, where the team led by pediatrician Beniam Tadewos Lamboro took a closer look at what her body was actually doing.

On admission, the physical examination offered the first decisive clues. The baby showed severe intercostal and subcostal retractions, the visible sinking of the chest wall between and beneath the ribs as she struggled to move air. More tellingly, auscultation revealed completely absent air entry on the left side of her chest. A silent hemithorax in a newborn is an alarming finding that demands an immediate explanation, whether that explanation is fluid, collapse, a diaphragmatic hernia, or the absence of lung tissue itself. The examining team recognized that a simple infection could not account for everything they were hearing and seeing.

Chest radiography then sharpened the picture considerably. The X-ray showed opacities in the right middle and lower lobes with air bronchograms, findings consistent with pneumonia, confirming that the infection was real. But it also showed complete opacification of the left hemithorax, together with two features that pointed away from infection and toward a structural problem: crowding of the ribs on the left side and a shift of the mediastinum, the central compartment of the chest containing the heart and great vessels, toward the left. These are classic signs of volume loss. When lung tissue is absent or collapsed, the structures around it fill the void, and the chest wall and mediastinum migrate toward the affected side. In pneumonia, by contrast, the affected side tends to hold its volume or even expand. The combination of infection on one side and volume loss on the other raised the suspicion of a congenital lung anomaly coexisting with pneumonia.

To settle the question, the team performed contrast-enhanced computed tomography of the chest. The CT scan delivered an unambiguous answer: the left main bronchus, the left lung, and the left pulmonary artery were completely absent. There was no vestige of left-sided pulmonary architecture at all. The scan also measured the ratio of the main pulmonary artery diameter to the aortic diameter, which exceeded 1, a radiographic marker associated with elevated pulmonary vascular resistance and pulmonary hypertension. This finding mattered enormously for prognosis and management, because it signaled that the single right lung was not only doing all the oxygenation work but was also facing abnormally high pressures in its circulation.

Echocardiography completed the hemodynamic assessment and revealed the downstream consequences of the missing lung. The right side of the heart, which pumps blood into the pulmonary arteries, was enlarged, a predictable consequence of pumping against increased resistance. The baby had a patent ductus arteriosus, a persistent fetal blood vessel connecting the aorta and the pulmonary artery, measuring 2.5 millimeters with bidirectional shunting, meaning blood was flowing back and forth across it rather than in a single direction. She also had severe tricuspid regurgitation, a leak of the valve between the right atrium and right ventricle, with a peak pressure gradient of 62 millimeters of mercury, a value that indicated severe pulmonary hypertension. In essence, the vascular bed of the lone right lung could not accommodate the entire cardiac output at normal pressures, and the heart was straining against that limitation.

Management proceeded along two parallel tracks. The team supported the infant’s breathing with continuous positive airway pressure, or CPAP, which keeps the airways and air sacs propped open and reduces the work of breathing without requiring invasive ventilation. At the same time, she received medical therapy aimed at lowering pulmonary vascular resistance and supporting cardiac function. This combination reflects the modern understanding of pulmonary agenesis as a cardiopulmonary condition rather than a purely anatomical one: the missing lung is fixed, but the pressures in the pulmonary circulation and the strain on the right heart are potentially modifiable with drugs. Notably, the infant survived the neonatal period, a stage at which many cases of pulmonary agenesis historically proved fatal.

Follow-up over the first nine months of life told a nuanced story. At six months, the child remained dependent on supplemental oxygen but had achieved age-appropriate growth and developmental milestones, an outcome the authors emphasize as meaningful given the severity of her initial presentation. Repeat echocardiography, however, showed that the patent ductus arteriosus had enlarged to 6 to 7 millimeters with persistent bidirectional shunting, indicating that the pulmonary vascular disease had not resolved and may have progressed. By nine months of age she was still on home oxygen and continuing medical therapy, but she had required no further hospitalizations. The report thus documents both the resilience of a child living with a single lung and the chronic, evolving nature of the pulmonary hypertension that accompanies it.

The authors draw a clear practical conclusion from this single case. Congenital lung agenesis can coexist with ordinary respiratory infections, and those infections can mask the underlying anomaly, delaying diagnosis and appropriate counseling. They argue that clinicians in resource-limited settings, where advanced imaging is not always available at first contact, should suspect congenital lung anomalies whenever a neonate or infant presents with persistent respiratory distress accompanied by radiographic signs of volume loss, specifically mediastinal shift and rib crowding on chest radiography. In such circumstances, they recommend considering CT imaging for confirmation. The case is also a broader argument for the value of publishing detailed clinical observations from settings where rare diseases are underreported: every documented case sharpens the pattern recognition of clinicians who may otherwise encounter such a presentation only once in a career, and for the family in this report, that sharpened recognition is what transformed a treatment-resistant pneumonia into a defined, manageable diagnosis.

Subject of Research: A rare case of neonatal left lung agenesis initially misdiagnosed as pneumonia in a resource-limited setting

Article Title: Neonatal left lung agenesis presenting as pneumonia in a resource-limited setting: a case report

Article References: Lamboro, B. T., Girma, S. M., Temesgen, N. E., Mengistu, A. G., & Mamo, Z. B. (2026). Neonatal left lung agenesis presenting as pneumonia in a resource-limited setting: a case report. BMC Pediatrics. https://doi.org/10.1186/s12887-026-07723-4

Image Credits: AI Generated

DOI: 10.1186/s12887-026-07723-4

Keywords: lung agenesis, neonatal respiratory distress, congenital anomalies, pulmonary hypertension, pneumonia, patent ductus arteriosus, chest CT, echocardiography, resource-limited settings, neonatology, case report, BMC Pediatrics

The clinical stakes are considerable. Bronchopulmonary dysplasia, defined by the need for supplemental oxygen or respiratory support at a corrected gestational age of thirty-six weeks, affects a substantial proportion of infants born before twenty-eight weeks of gestation and is associated with long-term respiratory morbidity, neurodevelopmental impairment, and rehospitalization throughout childhood. Its pathogenesis is multifactorial, involving inflammation, infection, hyperoxia exposure, impaired alveolar and vascular development, and genetic and environmental interactions. Because no single therapy has proven reliably protective, clinicians scrutinize every drug that reaches the developing lung for possible harm, and the analgesics and anti-inflammatory agents used in the first weeks of life are no exception.

The story of these drugs in the neonatal intensive care unit begins with the ductus arteriosus itself. Increased blood flow across a patent ductus arteriosus can be associated with increased pulmonary blood circulation and morbidity, a hemodynamic burden that physicians have tried to relieve since the latter part of the twentieth century by closing a hemodynamically significant ductus in the hope of improving outcomes. The pharmacological workhorses of that effort have been cyclooxygenase inhibitors, chiefly indomethacin and ibuprofen, which reduce prostaglandin signaling and allow the vessel to constrict and close. Both drugs have been used extensively for ductal closure, but both carry side effects and safety concerns in preterm infants, including effects on renal perfusion, gastrointestinal integrity, and platelet function, concerns that have driven a decades-long search for alternatives.

That search produced one of the more memorable accidental discoveries in modern neonatology. As recounted by Sharma and Bhandari, Hammerman and colleagues observed that the use of acetaminophen in preterm infants led to closure of the patent ductus arteriosus, a finding reported in case series that surprised many observers. The mechanism is plausible: acetaminophen acts on prostaglandin synthesis through pathways distinct from classical cyclooxygenase inhibition, and the ductus in the preterm infant remains sensitive to even modest reductions in prostaglandin activity. Following those initial case reports, multiple trials demonstrated that acetaminophen was as effective in closing the ductus as the two established non-steroidal anti-inflammatory drugs, ibuprofen and indomethacin. Crucially, those studies did not look only at closure rates; they also examined associated morbidities, and bronchopulmonary dysplasia emerged as the outcome of greatest interest.

The evidence on that outcome, however, has been reassuringly consistent so far. A large multicenter trial conducted by Gupta and colleagues, published in the New England Journal of Medicine, showed no significant difference in the incidence of bronchopulmonary dysplasia between groups of infants treated with ibuprofen and those given placebo. A retrospective study by Jensen and colleagues compared one group of infants receiving acetaminophen with another receiving ibuprofen or indomethacin and found that the incidence of death or grade 2 to 3 bronchopulmonary dysplasia was similar in both groups. These findings suggested that neither class of drug, when used for ductal closure, clearly worsens the risk of chronic lung disease, at least within the populations and dosing regimens studied.

The BeNeDuctus trial added an important dimension to this debate. This large multicenter randomized non-inferiority trial compared expectant management of a significant patent ductus arteriosus, meaning careful observation without immediate drug treatment, against early treatment with ibuprofen. The trial showed no difference in the incidence of bronchopulmonary dysplasia, necrotizing enterocolitis, or death between the two management strategies. That result was consequential in its own right, because it suggested that routine early pharmacological closure of the ductus may not be necessary for all affected infants. But it also created an unexpected opportunity: some patients in both subgroups received acetaminophen, not for ductal closure but for analgesia, meaning the trial inadvertently enrolled a cohort of extremely preterm infants exposed to the drug for reasons unrelated to their ductus.

Hoornenborg and colleagues exploited that opportunity in their secondary analysis, asking whether paracetamol given as an analgesic was associated with an increased risk of bronchopulmonary dysplasia in extremely preterm infants. The question matters because acetaminophen is among the most widely administered medications in neonatal intensive care, used for procedural and postoperative pain and increasingly considered for ductal closure. If the drug carried even a modest risk to the developing lung, the population-level consequences could be substantial given how many preterm infants receive it. Sharma and Bhandari frame their commentary around exactly this tension between therapeutic utility and pulmonary safety.

Concern about acetaminophen’s effects on the lung is not merely theoretical. Laboratory studies referenced in the commentary have shown that toxic acetaminophen exposure can induce distal lung endoplasmic reticulum stress, proinflammatory signaling, and emphysematous changes in the adult murine lung, and that the developing murine lung appears susceptible to acetaminophen toxicity in ways independent of the hepatic damage for which the drug is best known. Investigators have also raised the possibility that acetaminophen exposure in early life could have lifelong consequences for respiratory health. On the other side of the ledger, ibuprofen has its own pulmonary profile: animal work has documented vascular and pulmonary effects of ibuprofen on neonatal lung development, and recent studies indicate that inhibition of the mitochondrial integrated stress response can ameliorate ibuprofen-induced endothelial dysfunction in models of neonatal hyperoxia-induced lung injury. Both drug classes, in other words, have biological plausibility for lung effects that clinical trials have so far not translated into clear harm.

Interpreting this literature requires attention to the difficulty of the outcome itself. Bronchopulmonary dysplasia is now understood as a syndrome with multiple pulmonary phenotypes in the preterm infant, and its diagnosis has been refined through evidence-based approaches that grade severity by the level of respiratory support required. Newer tools, including magnetic resonance imaging phenotyping and life-course approaches to lung function monitoring after preterm birth, are reshaping how researchers detect subtle drug effects that survival-based or oxygen-based definitions may miss. The commentary’s authors, who have previously argued that bronchopulmonary dysplasia research must move from the bedside to the bench and back again, emphasize that postnatal inflammation, corticosteroid effects on lung development, and gene-environment interactions all complicate any attempt to isolate the contribution of a single analgesic or anti-inflammatory drug.

Where does this leave clinicians and families? The accumulating trial evidence, from the Gupta ibuprofen trial, the Jensen retrospective comparison, the BeNeDuctus trial, and now the Hoornenborg secondary analysis, points toward a consistent conclusion: neither acetaminophen nor the classical non-steroidal anti-inflammatory drugs, as used in contemporary neonatal practice, has been shown to increase the incidence of bronchopulmonary dysplasia or death in extremely preterm infants. At the same time, Sharma and Bhandari’s commentary underscores that the question of pulmonary safety has not been closed as definitively as the ductus itself. Preclinical signals of lung toxicity, the heterogeneity of bronchopulmonary dysplasia phenotypes, and the possibility of long-term respiratory consequences all argue for continued vigilance. As randomized trials of prophylactic acetaminophen for ductal closure and expectant management strategies continue to mature, the developing lung remains the outcome against which every neonatal drug must ultimately be judged.

Subject of Research: Pulmonary safety of acetaminophen and NSAID treatment for patent ductus arteriosus in preterm infants

Article Title: Does use of acetaminophen and/or NSAIDs increase the risk of developing bronchopulmonary dysplasia?

Article References: Sharma, R., & Bhandari, V. (2026). Does use of acetaminophen and/or NSAIDs increase the risk of developing bronchopulmonary dysplasia?. Pediatric Research. https://doi.org/10.1038/s41390-026-05526-y

Image Credits: AI Generated

DOI: 10.1038/s41390-026-05526-y

Keywords: bronchopulmonary dysplasia, acetaminophen, NSAIDs, patent ductus arteriosus, preterm infants, BeNeDuctus trial, neonatology, ibuprofen, indomethacin, Pediatric Research, lung development, neonatal intensive care

Current guidance from pediatric and cardiovascular societies generally favors intervention for “high-volume” hsPDAs that persist beyond about 10–14 days after unsuccessful conservative care or failed pharmacologic therapy. Intervention is also recommended when medications are contraindicated, such as when specific clinical contraindications limit exposure to indomethacin or ibuprofen. These recommendations are consensus-based and aim to balance ductal persistence against the hazards of catheter procedures.

However, direct evidence pinpointing the optimal day to place the device remains scarce. Much of the available literature is observational, with substantial variation in inclusion criteria, ductal severity definitions, procedural technique, and infant baseline risk. As a result, studies often struggle to distinguish whether outcomes reflect timing itself or differences in illness severity that drive clinicians’ decisions.

The review emphasizes how timing may influence the biology of the ductus and the infant’s physiology. Delayed closure could allow ongoing left-to-right shunting, exposing organs to altered perfusion and inflammation. In contrast, earlier closure may occur before the infant’s pulmonary, hemodynamic, or coagulation status fully stabilizes, potentially increasing risks such as vascular access complications, device malposition, or post-procedural instability.

A key uncertainty is how timing affects morbidity trajectories. Clinicians care about outcomes including bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis, need for ongoing ventilation, and longer-term growth or cardiovascular adaptation. The review highlights that timing-related effects could be mediated by both shunt duration and the infant’s evolving capacity to tolerate interventions.

Ongoing trials are expected to provide stronger evidence by testing structured timing strategies and standardizing outcome measures. In the meantime, the authors propose a clinical decision framework: incorporate ductal hemodynamic burden, response—or lack of response—to medical therapy, gestational age, procedural feasibility, and evolving organ function, rather than relying on ductus duration alone.

The overarching message is that “early versus late” is not a single answer. Individualization may be necessary because infant fragility, ductal anatomy, and institutional expertise all interact with when closure is attempted. The field’s priority is to translate future trial results into actionable timing thresholds that reliably reduce morbidity without escalating procedural harm.

Ultimately, optimizing when device occlusion occurs could help shift practice from guideline-driven timing to evidence-based timing. That transition may improve survival and reduce avoidable neonatal complications by aligning intervention with both ductal persistence and infant readiness.

Subject of Research: Pediatric transcatheter device occlusion timing in preterm infants with hsPDA.
Article Title: Optimal timing for transcatheter device occlusion of a hemodynamically significant patent ductus arteriosus in preterm infants: evidence, uncertainty, and future directions.
Article References: Avades, M.J., Griffiths, P.S., Weems, M.F. et al. J Perinatol (2026). https://doi.org/10.1038/s41372-026-02816-5
Image Credits: AI Generated
DOI: https://doi.org/10.1038/s41372-026-02816-5
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