The research, published in the Journal of Perinatology, was led by nutrition scientist Lyssa Lamport of Rutgers University together with colleagues at Cohen Children’s Medical Center of New York. The team carried out a retrospective cross-sectional chart review of 359 very low birth weight infants born at less than 32 weeks gestation between January 2021 and December 2024. Their goal was to determine whether the type of human milk an infant received during the earliest phase of enteral nutrition influenced three key measures of neonatal feeding progress: the number of days until human milk fortification was added, the number of days until full enteral nutrition was achieved, and the total duration of parenteral nutrition, in which nutrients are delivered intravenously.

The stakes of these milestones are far from abstract. Human milk is widely regarded as the gold standard for feeding premature infants, and an exclusive human milk diet has been linked to significant reductions in prematurity-related complications such as necrotizing enterocolitis, a potentially devastating bowel disease, and late-onset sepsis, a bloodstream infection. Reaching full enteral nutrition as quickly and safely as possible is also essential because prolonged reliance on intravenous nutrition carries its own risks, including infection and liver injury. Feeding milestones and parenteral nutrition duration therefore serve as critical indicators of an infant’s maturation and overall development.

Yet mother’s own milk and donor milk are not biologically identical. Mother’s own milk, particularly in the earliest days after birth, is a dynamic biological fluid packed with bioactive components that support immune protection and intestinal maturation. Colostrum, the first milk produced after delivery, contains the highest concentration of these factors, which gradually decline as milk matures. Donor milk, by contrast, is typically collected from mothers of older infants and contains lower levels of protein, fat, and bioactive components. The Holder pasteurization process required for safety further reduces immune cells, anti-inflammatory factors, and beneficial bacteria, leaving mainly heat-stable components at diminished concentrations. These disparities have raised persistent questions about whether donor milk can truly substitute for a mother’s own colostrum and milk during the most vulnerable window of a preterm infant’s life.

The urgency of answering that question has grown alongside the explosive expansion of donor milk use. In advanced-level neonatal care units in the United States, donor milk utilization rose from 28.7 percent in 2009 to 54.7 percent in 2020, and by 2024 it exceeded 95 percent. Many units now initiate early enteral feeding with donor milk while waiting for a mother’s milk supply to come in, a practice designed to avoid formula but one that may inadvertently limit a newborn’s exposure to colostrum. Despite this widespread adoption, few studies have directly compared exclusive mother’s own milk, exclusive donor milk, and mixed feeding regimens, largely because infants in donor milk groups are usually also fed some maternal milk, making it impossible to isolate the effects of an exclusively donor milk diet.

The New York team took advantage of a setting in which the two milks were fed separately and meticulously recorded, allowing exact calculation of each infant’s intake. They classified infants into four groups based on the proportion of mother’s own milk versus donor milk received from the first enteral feed until fortification: 100 percent mother’s own milk, 100 percent donor milk, donor milk with at least 50 percent maternal milk, and donor milk with less than 50 percent maternal milk. The study period for this classification deliberately ended at the time of fortification, providing a standardized window for evaluating early, unfortified milk exposure. Infants who had received any formula, who had not begun enteral feeding within 72 hours of life, or who had developed serious bowel complications before the first feed were excluded, along with infants transferred in after 24 hours of life and those with congenital anomalies or metabolic disorders.

The cohort was typical of modern neonatal intensive care populations. Median gestational age was 28.9 weeks, mean birth weight was about 1060 grams, and slightly more than half the infants were female. The first enteral feed was initiated on average at roughly 36 hours of life, and nearly half of the infants received mother’s own milk as that first feed. About 30 percent received exclusive maternal milk during the study window, 11 percent received exclusive donor milk, and the remaining 59 percent received a mixture. Across the whole cohort, fortification was added at a median of five days, full enteral nutrition was reached at nine days, and parenteral nutrition lasted a median of ten days.

When the researchers analyzed the data using a generalized linear model with a negative binomial distribution, appropriate for overdispersed count data, and adjusted for birth weight, five-minute APGAR score, intrauterine growth restriction, and the hour of the first feed, the results were unambiguous. No statistically significant differences emerged among the milk type groups for days to fortification, days to full enteral nutrition, or days of parenteral nutrition. The P values ranged from 0.70 to 0.79, far from the threshold of significance. This finding directly contradicted the team’s original hypothesis that starting with 100 percent donor milk would delay feeding milestones and prolong intravenous nutrition.

The unadjusted data told a more complicated and instructive story. Before statistical correction, infants fed exclusively mother’s own milk appeared to take longer to reach fortification, full feeding, and independence from parenteral nutrition, and they had the longest hospital stays. But that group also had the lowest mean birth weight, at about 989 grams, and a higher rate of low five-minute APGAR scores, suggesting they were simply smaller and sicker from the start. Previous research has shown that each one-week decrease in gestational age, each 100-gram drop in birth weight, or each point lower on the five-minute APGAR score raises the likelihood of delayed feeding advancement by eight to twenty percent. Once these confounders were accounted for, the apparent disadvantage of maternal milk vanished, underscoring how profoundly an infant’s underlying condition shapes feeding outcomes regardless of milk source.

The authors emphasize that their findings offer practical reassurance for clinicians and families alike: prioritizing human milk feeding, including an exclusive donor milk diet, does not impede feeding progression or extend the need for intravenous nutrition. The results reinforce recommendations from the American Academy of Pediatrics and the World Health Organization to maximize human milk feeding in preterm infants, using donor milk when maternal milk is insufficient or unavailable, and they strengthen the case for integrating donor milk programs into standard neonatal protocols. At the same time, the study leaves important questions open. A compelling but statistically underpowered trend showed that infants receiving higher proportions of maternal milk were more likely to receive colostrum before tube feeding began and had the lowest rates of necrotizing enterocolitis, consistent with a dose-dependent protective effect. Because the study was retrospective and cross-sectional, causality cannot be established, and it examined only short-term feeding milestones rather than growth, neurodevelopment, or long-term immune outcomes. The authors call for larger, adequately powered prospective studies to determine whether an exclusive donor milk diet, in the absence of early colostrum exposure, might still compromise protection against necrotizing enterocolitis and to explore how milk type interacts with degrees of prematurity and growth restriction. For now, the central message stands: in the race to full feeding, what matters most may be that preterm infants receive human milk at all.

Subject of Research: Effects of mother's own milk versus donor human milk on neonatal feeding milestones in preterm infants

Article Title: Early enteral nutrition with mothers’ own milk, donor human milk, or a combination of both on neonatal feeding milestones: a cross-sectional study

Article References: Lamport, L., Samavat, H., Gomes, A., Newkirk, M., Byham-Gray, L., & Ziegler, J. (2026). Early enteral nutrition with mothers’ own milk, donor human milk, or a combination of both on neonatal feeding milestones: a cross-sectional study. Journal of Perinatology. https://doi.org/10.1038/s41372-026-02928-y

Image Credits: AI Generated

DOI: 10.1038/s41372-026-02928-y

Keywords: preterm infants, donor human milk, mother's own milk, enteral nutrition, parenteral nutrition, human milk fortification, necrotizing enterocolitis, very low birth weight, neonatal intensive care, colostrum, feeding milestones, Journal of Perinatology

Acute kidney injury, often abbreviated AKI, is far from rare in this population. Among infants born at less than 29 weeks of gestation, studies have reported incidence figures reaching as high as 38 to 48 percent. That staggering prevalence reflects the convergence of multiple hazards: immature nephrons that have not completed their developmental program, hemodynamic instability in the transitional period after delivery, and frequent exposure to medications that the developing kidney handles poorly. The consequences are not trivial. Neonates who experience early kidney injury face roughly threefold higher mortality and require substantially longer hospital stays than their peers who escape renal harm.

The clinical challenge has always been timing. Standard definitions of acute kidney injury rely on serum creatinine, a waste molecule that accumulates only after renal function has already deteriorated. In newborns, this creates a diagnostic lag of a day or more, because maternal creatinine must first clear from the infant’s circulation before the baby’s own values become interpretable. By the time a creatinine rise crosses the diagnostic threshold, the window for preventive intervention may have closed. This is precisely the gap that the STARZ score, first described by Schuh and colleagues in the Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates, or AWAKEN, dataset, was designed to close.

STARZ is an acronym that encodes its six components: Sex, birth weight Z-score, Risk of infection, and Zygosity, with each element contributing points toward a composite risk estimate. The score draws exclusively on information available within the first hours after birth, including whether the infant is male, how small the baby is relative to gestational age norms, the presence of maternal chorioamnionitis or other infection risk factors, and whether the infant is one of a multiple gestation. None of these variables requires a laboratory measurement of renal function, which means clinicians can calculate a risk category long before creatinine becomes informative.

In its original derivation, the STARZ score stratified neonates into low, medium, and high-risk categories with meaningful separation in observed AKI rates. The new commentary by Owens and Schuh addresses a question that determines whether such a tool can leave the research setting: does STARZ hold up when applied to fresh cohorts beyond the dataset in which it was born? Validation studies in very low birth weight populations, the authors note, are the essential next step, and the accumulating evidence suggests the score performs credibly when tested in independent samples of preterm infants.

The significance of external validation cannot be overstated. Prediction models are notoriously prone to optimism when evaluated on the very data used to build them, a phenomenon statisticians call overfitting. A score that discriminates beautifully in its derivation cohort may falter when confronted with patients from a different hospital, era, or case mix. For STARZ, the demonstration that its risk strata remain informative in very low birth weight neonates treated in the United States provides reassurance that the underlying physiology it captures, namely the interplay of developmental vulnerability, inflammatory stress, and perinatal compromise, is not an artifact of a single dataset.

What would change in practice if STARZ were adopted widely? The most immediate application is triage. Infants flagged as high risk on the first day of life could be targeted for intensified monitoring, including earlier and more frequent assessment of urine output, serum creatinine, and novel biomarkers such as urinary cystatin C or NGAL. Nephrotoxic medication regimens, particularly aminoglycosides and nonsteroidal anti-inflammatory drugs used to close patent ductus arteriosus, could be reviewed and adjusted in high-risk infants before renal injury becomes established. Fluid management strategies, which balance the dangers of dehydration against those of volume overload, could be calibrated to the individual infant’s renal risk profile rather than applied uniformly.

The commentary also situates STARZ within a broader movement toward precision neonatology. The AWAKEN registry, a multinational study that enrolled hundreds of neonates across dozens of centers, revealed that neonatal AKI is both common and underrecognized, with most cases missed by clinical teams relying on creatinine alone. Tools like STARZ represent the first generation of risk stratification instruments built specifically for this population, in contrast to adult-derived scores that translate poorly to the neonatal context. The authors emphasize that the score is intended to complement, not replace, clinical judgment and ongoing biochemical surveillance.

Limitations remain, and the commentary is candid about them. STARZ was derived from data collected in the 2010s, and neonatal care has evolved since then, with shifts in surfactant protocols, ventilation strategies, and antibiotic stewardship that could alter baseline AKI risk. The score also predicts risk at a population level rather than certifying certainty for any individual infant; a high-risk designation indicates elevated probability, not destiny. Furthermore, the components of STARZ capture perinatal and demographic factors but do not directly measure dynamic physiological variables such as evolving blood pressure trends or cumulative nephrotoxic exposure, which may refine prediction further in future iterations.

Nevertheless, the trajectory is clear and encouraging. A simple bedside calculation, performable within hours of birth using information already recorded in the chart, offers clinicians a head start against a complication that has historically been diagnosed only in retrospect. For the smallest and sickest infants, whose kidneys teeter between recovery and injury in their first week of life, that head start could translate into earlier interventions, fewer missed diagnoses, and ultimately improved survival. As validation evidence accumulates, STARZ may well become a standard element of the admission assessment for very low birth weight neonates, marking a quiet but consequential shift in how neonatal kidney disease is anticipated rather than merely treated.

Subject of Research: Risk prediction of acute kidney injury in very low birth weight preterm neonates using the STARZ scoring system

Article Title: STARZ Scoring in Very Low Birth Weight (VLBW) neonates: validation and risk-stratification for neonatal acute kidney injury

Article References: Owens, J., & Schuh, M. P. (2026). STARZ Scoring in Very Low Birth Weight (VLBW) neonates: validation and risk-stratification for neonatal acute kidney injury. Pediatric Research. https://doi.org/10.1038/s41390-026-05557-5

Image Credits: AI Generated

DOI: 10.1038/s41390-026-05557-5

Keywords: neonatal acute kidney injury, STARZ score, very low birth weight, preterm infants, AWAKEN study, risk prediction, serum creatinine, nephrotoxic medications, neonatal intensive care, kidney biomarkers, precision neonatology, external validation

Cytomegalovirus, a member of the herpesvirus family, is among the most common viral infections encountered in the newborn period. International consensus distinguishes two forms by timing: virus detected within the first three weeks after birth indicates congenital infection acquired in the womb, while a negative result in those first weeks followed by a positive result later defines postnatal infection. In full-term infants, postnatal cytomegalovirus is usually silent. In very preterm or very low birth weight infants, however, the virus can cause sepsis-like illness, pneumonia, hepatitis, colitis, thrombocytopenia, neutropenia, and even death. Capillary leak syndrome, a condition in which plasma escapes the circulation into surrounding tissues, has only rarely been linked to this infection in neonates.

The infant in the report was one of twins born after premature rupture of membranes, weighing just 1,475 grams at birth. His mother carried antibodies to cytomegalovirus but showed no evidence of active infection during pregnancy. Testing at two weeks of age found no viral immunoglobulin M and no viral DNA in his urine, confirming that he had not been infected in utero. After an initial 42-day hospital stay, during which he received albumin infusions for low blood protein but no other blood products, he went home feeding well on fortified breast milk, reaching 2,260 grams.

The turning point came at 57 days of life, when he developed an intermittent cough and small petechial hemorrhages on his upper arms. By day 63 he was in respiratory distress and was readmitted to his birth hospital. Laboratory tests revealed a striking constellation: elevated white blood cells, falling platelets, and liver enzymes dramatically elevated, with alanine aminotransferase at 196 units per liter and aspartate aminotransferase at 467. Serum tested positive for cytomegalovirus immunoglobulin M, and viral DNA was detectable in both blood and urine. Cultures of blood and cerebrospinal fluid came back sterile, pointing away from bacterial meningitis or septicemia.

His respiratory failure escalated rapidly despite nasal cannula oxygen, continuous positive airway pressure, and noninvasive intermittent ventilation, forcing doctors to intubate him at 70 days of life. When he arrived at Hebei Children’s Hospital three days later, he was receiving 80 percent oxygen, his skin was mottled and swollen, and petechiae covered his body. Clinicians calculated his fluid overload at 32 percent of his admission body weight, a figure that would climb to 53.3 percent as edema worsened. Ultrasound and radiography revealed massive pleural effusions and ascites, while echocardiography documented a patent ductus arteriosus and severe pulmonary hypertension estimated at approximately 84 millimeters of mercury.

Viral load measurements told the story with unusual clarity. Real-time quantitative polymerase chain reaction detected more than 570,000 copies of cytomegalovirus DNA per milliliter of blood, with high levels also in urine, sputum, ascitic fluid, and pleural fluid. Crucially, the mother’s breast milk contained viral DNA at 1,934 copies per milliliter, and the infant had received no blood products other than albumin, making breastfeeding the most probable route of transmission. Every bacterial and fungal culture was negative, as were assays for beta-D-glucan, galactomannan, and Mycobacterium tuberculosis, effectively eliminating competing diagnoses. The team concluded the infant had postnatal cytomegalovirus infection complicated by sepsis, severe capillary leak syndrome, pulmonary hypertension, and shock.

The pathophysiology of capillary leak syndrome centers on endothelial injury. A hyperinflammatory insult damages the single-cell lining of capillaries, opening gaps that allow protein-rich plasma to flood into the interstitial space. Damaged endothelial cells themselves secrete proinflammatory cytokines, creating a self-reinforcing loop of vascular permeability. The classical triad is hemodynamic instability, intravascular hypovolemia, and generalized edema. Some researchers argue that microvascular leakage is not merely a complication of sepsis but a central driver of its mortality, a reframing that makes recognition of the syndrome in neonates critically important.

Treatment began along conventional lines: mechanical ventilation with inhaled nitric oxide for the pulmonary hypertension, dopamine to support blood pressure, plasma and platelet transfusions, and intravenous ganciclovir at 6 milligrams per kilogram every twelve hours. Despite these measures, urine output collapsed to 0.59 milliliters per kilogram per hour, body weight surged, and acute kidney injury set in. At 77 days of life the team initiated continuous renal replacement therapy in continuous veno-venous hemofiltration mode, using a catheter in the right internal jugular vein, heparin anticoagulation, a modest blood flow of 12 to 14 milliliters per minute, and ultrafiltration rates of 5 to 15 milliliters per hour. Over 51 hours the circuit removed 530 milliliters of fluid. Urine output rebounded to 3.5 milliliters per kilogram per hour, the edema receded, and the therapy was stopped.

Recovery was protracted but ultimately complete. The infant received three weeks of intravenous ganciclovir followed by two weeks of oral valganciclovir until blood viral DNA fell below the assay’s detection limit. A chest tube placed for the pleural effusion came out at 86 days, and mechanical ventilation ended the following day. He spent 52 days in the hospital before discharge at 125 days of life. Follow-up showed a brief viral rebound and months of abnormal liver enzymes and low platelets, but by nine months of age every laboratory parameter had normalized. Neurodevelopmental assessment at 18 months using the Gesell Developmental Schedules yielded scores between 87 and 93 across five domains, indicating normal development.

The case carries several lessons for neonatal practice. Breast milk transmission is the dominant source of postnatal cytomegalovirus in units that use leukoreduced, seronegative blood products, and a systematic review estimates that roughly 20 percent of very low birth weight infants acquire the virus this way, with 3.7 percent developing symptomatic disease. Some countries pasteurize milk for the smallest infants, though the practice remains debated because it destroys beneficial milk components. The authors argue that postnatal cytomegalovirus can precipitate life-threatening capillary leak syndrome and that clinicians should consider continuous renal replacement therapy early when antiviral drugs, fluid management, and circulatory support fail to control runaway fluid overload. They also call for larger prospective studies to define the optimal timing of antiviral treatment in this vulnerable population, noting that clinical vigilance for this rare but devastating complication remains insufficient.

Subject of Research: Severe capillary leak syndrome caused by postnatal cytomegalovirus infection in a very preterm infant, treated with continuous renal replacement therapy

Article Title: Severe capillary leak syndrome caused by postnatal cytomegalovirus infection in a very preterm infant: a case report

Article References: Fang, J., Chen, X., Li, T., Cao, L., & Ma, L. (2026). Severe capillary leak syndrome caused by postnatal cytomegalovirus infection in a very preterm infant: a case report. Frontiers in Pediatrics, 14, Article 1895522. https://doi.org/10.3389/fped.2026.1895522

Image Credits: AI Generated

DOI: 10.3389/fped.2026.1895522

Keywords: cytomegalovirus, capillary leak syndrome, preterm infant, breast milk transmission, neonatology, continuous renal replacement therapy, acute kidney injury, ganciclovir, very low birth weight, sepsis, pulmonary hypertension, neonatal intensive care

Peripherally inserted central catheters, universally abbreviated as PICCs, are thin, flexible tubes threaded from a peripheral vein until the tip rests near the heart. In extremely low birth weight and very low birth weight infants, babies born weighing under 1,500 grams and often under 1,000 grams, these catheters are the primary vehicle for parenteral nutrition, the glucose, amino acids, lipids, and electrolytes delivered directly into the bloodstream when the immature gut cannot yet absorb enough nourishment. Because these infants are so small, their total daily fluid allowance is astonishingly restricted, sometimes only a few tens of milliliters per kilogram of body weight, which means every milliliter of the infusion must be carefully budgeted.

Herein lies the problem that motivated the research team led by Jian Cao of Shanghai Children’s Hospital and colleagues at the Second People’s Hospital of Kashi in Xinjiang, China. Many neonatal units enforce a conventional minimum infusion rate of 3 milliliters per hour through PICCs, based on the empirical belief that slower flows allow blood, lipid deposits, or precipitated minerals to stagnate inside the catheter lumen and trigger occlusion. But as a preterm infant matures and enteral feeding through the gut increases, the amount of parenteral nutrition the baby actually needs shrinks. If the pump cannot be set below 3 milliliters per hour, the infusion may deliver more fluid than the baby can tolerate, forcing clinicians to stop parenteral nutrition altogether and run the catheter on maintenance fluid instead, a practice known as functional idling. During such idling, the baby loses the nutritional stream that the catheter was placed to provide.

The study, published on 9 October 2026, took the form of a retrospective before-after cohort evaluation at a single center. The researchers compared 64 extremely or very low birth weight infants admitted during 2025, when the unit adopted a minimum infusion rate of 2 milliliters per hour, with a historical control group of 54 comparable infants treated during 2024 under the traditional 3 milliliter per hour threshold. To keep the comparison as clean as possible, the team applied a strict inclusion criterion requiring a confirmed central tip location for every catheter, and both groups followed identical, unified catheter maintenance protocols. Baseline characteristics of the two cohorts were statistically comparable, with no significant differences reported across the measured variables.

The primary safety question was catheter occlusion, the feared complication in which the lumen becomes blocked and the catheter must be removed prematurely. Using Fisher’s exact test, the investigators found no statistically significant difference between the groups: occlusion occurred in 6.2 percent of catheters in the lower-rate group versus 7.4 percent in the conventional group, a risk difference of minus 1.2 percentage points with a 95 percent confidence interval stretching from minus 12.0 to plus 8.7 percentage points. As a sensitivity analysis, the team applied Firth’s penalized logistic regression, a statistical technique designed for small samples and rare events that produces more stable estimates when ordinary logistic regression would struggle, and again found no signal of harm.

Secondary outcomes pointed in the same reassuring direction. Unplanned catheter removal, an indicator of complications severe enough to force the line out early, occurred in 4 of 64 catheters, or 6.2 percent, in the intervention group compared with 8 of 54, or 14.8 percent, in the control group, a difference that did not reach statistical significance with a P value of 0.14. Catheter-related bloodstream infection, the other major safety concern with any central line, was observed in none of the 64 intervention catheters versus 2 of 54, or 3.7 percent, of control catheters, again not statistically significant. The direction of these differences, while not conclusive, offered no evidence that the slower infusion rate endangered the infants.

The exploratory process and outcome measures, however, told a striking story. Functional idling, the proportion of catheters forced into a nutrition-free holding pattern, plummeted from 57.4 percent in the conventional-rate period to 18.8 percent in the lower-rate period, a difference the authors reported as highly significant. The median duration over which parenteral nutrition could be delivered through the PICC lengthened from 11.5 days, with an interquartile range of 7.0 to 16.0 days, to 14.0 days, with an interquartile range of 12.0 to 16.2 days, a difference with a P value of 0.002. Most compellingly for anyone who has watched a premature infant struggle to grow, the daily weight gain velocity rose from 11.99 plus or minus 1.82 grams per kilogram per day to 13.27 plus or minus 1.69 grams per kilogram per day, a statistically significant improvement. The authors are careful to note that these three variables are exploratory and partly determined by the infusion-rate policy itself, meaning the design cannot prove that the rate change directly caused the nutritional gains, but the physiological logic is coherent: allowing the pump to run slower lets clinicians keep delivering nutrition within the baby’s tight fluid budget for more days.

The technical reasoning behind why slower flows might block catheters deserves scrutiny, because the study’s null finding on occlusion challenges a widely held assumption. Catheter occlusion in neonates is typically attributed to fibrin sheaths forming around the catheter tip, blood refluxing into the lumen between flushes, precipitation of calcium and phosphate from the nutrition solution, or lipid deposits from fat emulsions. The traditional thinking held that a minimum flow of 3 milliliters per hour keeps the lumen sufficiently flushed to prevent stagnation. The new data suggest that at 2 milliliters per hour, with the same maintenance and flushing protocols in place, this stagnation effect either does not materialize or is too small to detect in a cohort of this size. It is worth emphasizing that the confidence interval around the occlusion risk difference was wide, spanning roughly 12 percentage points in either direction, so a modest true increase in occlusion risk cannot be excluded by this study alone.

Indeed, the authors are unusually candid about the limits of their evidence. The study was explicitly not powered to establish safety, equivalence, or non-inferiority; it was designed as a hypothesis-generating, exploratory evaluation of a practice change already adopted in many units worldwide, where rates of 1 to 2 milliliters per hour are used despite the absence of rigorous supporting trials. The before-after design introduces its own vulnerabilities, since temporal changes in staffing, patient mix, or co-interventions between 2024 and 2025 could theoretically have influenced outcomes, although the comparable baseline characteristics and unified maintenance protocols mitigate some of these concerns. The single-center setting in Kashi, Xinjiang, also raises the standard question of generalizability to units with different patient populations, formulations, and nursing practices.

What makes this study resonate beyond its modest sample size is the way it illuminates a quiet gap between clinical practice and clinical evidence. Neonatal teams around the world have been lowering minimum infusion rates on physiological intuition, trading a theoretical occlusion risk for the tangible benefit of sustained nutrition during the most growth-critical weeks of life. This exploratory cohort now offers the first structured comparison suggesting that the trade may be favorable, with lower idling rates, longer nutrition delivery, and faster weight gain at no detectable cost in catheter complications. The authors call for an adequately powered prospective non-inferiority trial to confirm the finding, and such a trial would need to enroll hundreds of infants to narrow the confidence intervals enough to rule out a clinically meaningful occlusion increase. Until then, the study stands as a careful, honest data point in a debate that directly touches the growth and survival of the smallest patients in medicine, and a reminder that in neonatal care, even a single milliliter per hour can carry the weight of a scientific question.

Subject of Research: Minimum infusion rate safety for peripherally inserted central catheters in extremely and very low birth weight preterm infants receiving parenteral nutrition

Article Title: Safety of a 2 mL/h minimum infusion rate for peripherally inserted central catheters in preterm infants: an exploratory single-center before-after cohort study

Article References: Cao, J., Liu, H., Zhang, W., Zhang, C., Ge, A., & Li, J. (2026). Safety of a 2 mL/h minimum infusion rate for peripherally inserted central catheters in preterm infants: an exploratory single-center before-after cohort study. BMC Pediatrics. https://doi.org/10.1186/s12887-026-07784-5

Image Credits: AI Generated

DOI: 10.1186/s12887-026-07784-5

Keywords: peripherally inserted central catheter, preterm infants, parenteral nutrition, minimum infusion rate, catheter occlusion, extremely low birth weight, very low birth weight, neonatal intensive care, catheter-related bloodstream infection, weight gain velocity, before-after cohort study, BMC Pediatrics

The research, conducted at Adana City Training and Research Hospital and published in BMC Pediatrics, analyzed 58 preterm infants who underwent a total of 63 catheterization episodes. The cohort was extraordinarily premature, with a median gestational age of 27 weeks and a median birth weight of just 900 grams. These are babies whose skin is translucent, whose lungs are still maturing, and whose veins are fragile enough that every invasive procedure carries disproportionate risk. For this population, the authors argue, the question of catheter tip location is not a technical nicety but a matter of immediate clinical safety, because a malpositioned catheter can cause vessel perforation, cardiac arrhythmia, pleural effusion, or the inadvertent infusion of hypertonic solutions into surrounding tissue.

The technique the team evaluated is conceptually simple. Instead of relying on a plain radiograph, in which the radiopaque catheter may be indistinguishable from overlapping bones and soft tissues, clinicians instill a small bolus of iohexol—a non-ionic, low-osmolar iodinated contrast agent available at concentrations of 300 or 350 milligrams of iodine per milliliter—directly through the catheter lumen. The contrast fills the catheter and briefly opacifies its full course, so the subsequent X-ray captures not just a faint line but a sharply defined trajectory from the insertion site all the way to the tip. The authors describe a characteristic radiographic appearance they call the butterfly sign, produced when adequate opacification of the catheter creates a winged pattern at the point where the device enters the vessel. When radiographs showed superposition of structures or the absence of this butterfly sign, the team considered the image suboptimal and repeated the procedure with additional contrast.

Defining success required an anatomical standard. For catheters inserted through the upper extremities, the target tip position was set between the second and fifth thoracic vertebral levels, corresponding to the lower superior vena cava or the cavoatrial junction. For lower extremity insertions, the acceptable range was between the ninth and tenth thoracic vertebral levels, where the catheter tip should rest within the inferior vena cava. These landmarks matter because the ideal tip location balances two competing hazards: a tip that is too peripheral increases the risk of phlebitis and thrombosis, while a tip that advances too far toward or into the heart can provoke arrhythmias or cardiac perforation. In adults, tip verification is routine; in infants weighing under a kilogram, the margin of error shrinks to a few millimeters, and the bony landmarks themselves are tiny and difficult to interpret.

The results revealed how far current practice falls short of that ideal. Only 20 percent of the catheters in the study were positioned at the predefined target level on initial placement. In other words, four out of five catheters required some form of correction or repositioning before they could be considered safely located. This striking figure underscores the central argument of the paper: without a reliable visualization method, clinicians may be unknowingly operating with malpositioned devices, and the true rate of malposition in ultrathin PICCs has likely been underestimated simply because plain radiography could not detect it. Contrast-enhanced imaging, by making the catheter’s path explicit, converts a guess into a measurement.

Efficiency of the technique also emerged as a key finding. Across the 63 catheterization episodes, the team performed 71 contrast administrations in total, meaning that a single dose was sufficient in 84 percent of cases. The remaining episodes required a second administration, typically because the initial radiograph failed to demonstrate adequate opacification or because the butterfly sign was absent. For a population in which every handling event carries stress, heat loss, and infection risk, the ability to confirm tip position with one dose and one image represents a meaningful advantage over repeated plain films or blind repositioning attempts.

Safety was, understandably, the most scrutinized dimension of the study. Iodinated contrast agents are well tolerated in adults, but preterm infants have immature renal function, small circulating blood volumes, and a thyroid gland that avidly takes up iodine, raising theoretical concerns about contrast-induced nephropathy and iodine-induced thyroid dysfunction. The researchers therefore monitored serum creatinine at three time points—baseline, 48 to 72 hours after contrast administration, and again at 3 to 7 days—and evaluated kidney injury using the KDIGO classification. Among the 45 catheterization episodes that could be fully evaluated for renal outcomes, stage 1 acute kidney injury occurred in five cases, an incidence of 11.1 percent. Importantly, the authors report no allergic reactions, no catheter occlusions attributable to the contrast, and no clinically significant contrast-related thyroid dysfunction during the observation period.

It is worth interpreting the renal findings with appropriate caution, as the authors themselves do. Stage 1 acute kidney injury is common in extremely preterm infants for many reasons unrelated to contrast exposure, including hypotension, respiratory distress syndrome, patent ductus arteriosus, necrotizing enterocolitis, and exposure to nephrotoxic medications. Without a matched control group of infants who received ultrathin PICCs without contrast, the 11.1 percent figure cannot be attributed to iohexol itself. The study’s retrospective, single-center design limits causal inference, and the authors are explicit that no evident short-term safety signal emerged in this cohort rather than claiming definitive safety. Larger, ideally prospective, comparative studies would be needed to quantify any true renal or thyroid risk attributable to the procedure.

Even with those caveats, the clinical implications are substantial. Ultrathin 1 French PICCs have become increasingly popular in neonatology precisely because they suit the smallest veins of micro-preemies, allowing parenteral nutrition and long-term intravenous therapy without the complications of repeated peripheral cannulation. But their adoption has outpaced the availability of reliable verification methods, and many units still rely on plain radiographs that may simply fail to show the device. The contrast-enhanced protocol described in this study offers a low-cost, widely accessible alternative that requires no special equipment beyond the contrast agent and standard radiography already present in any neonatal intensive care unit. The butterfly sign, in particular, gives clinicians a simple visual quality check: if the sign is absent, the image is not trustworthy, and the study should be repeated rather than acted upon.

The broader lesson of the study extends beyond one catheter type or one hospital. In modern medicine, devices are often miniaturized faster than the diagnostic tools needed to monitor them, and the gap is filled by improvisation. This research demonstrates that a deliberate, protocolized approach—defining anatomical targets, standardizing contrast doses, setting explicit criteria for image adequacy, and prospectively tracking renal function—can close that gap even in the most fragile patients. For the 900-gram infant whose catheter tip sits a few millimeters from the heart, the difference between an invisible line on an X-ray and a clearly opacified trajectory may be the difference between uneventful therapy and a catastrophic complication. As neonatal intensive care continues to push the boundaries of viability at ever lower gestational ages, techniques like contrast-enhanced radiography remind us that sometimes the most impactful innovations are not new devices at all, but better ways of seeing the ones already in place.

Subject of Research: Contrast-enhanced radiography for localizing ultrathin PICC tips in preterm infants

Article Title: Contrast-enhanced radiography for localization of ultrathin (1 F) PICCs in preterm infants: a retrospective observational study

Article References: Çeki̇nmez, E. K., Gülaşı, S., Demi̇r, O., Coşkun, H., & Bulut, H. Ç. (2026). Contrast-enhanced radiography for localization of ultrathin (1 F) PICCs in preterm infants: a retrospective observational study. BMC Pediatrics. https://doi.org/10.1186/s12887-026-07573-0

Image Credits: AI Generated

DOI: 10.1186/s12887-026-07573-0

Keywords: preterm infants, PICC, contrast-enhanced radiography, iohexol, catheter malposition, neonatology, NICU, acute kidney injury, butterfly sign, radiography, very low birth weight, catheter tip localization

The research, led by Sarah N. Kunz of Harvard Medical School and Beth Israel Deaconess Medical Center together with colleagues at Stanford University School of Medicine and the California Perinatal Quality Care Collaborative, examined data from California on very low birth weight, preterm infants born before 37 weeks of gestation who were less than 28 days old. The study period spanned 2012 through 2018, a window that captures a mature era of regionalized perinatal care in the nation’s most populous state. California offers a particularly valuable setting for this kind of analysis because of its sheer scale and the richness of its linked birth cohort records, which allow researchers to follow infants from birth through any subsequent acute transport between hospitals with unusual precision.

The design of the study was a retrospective cohort analysis, meaning the investigators looked backward at records that had already been generated by routine clinical care. Their outcome of interest was acute inter-hospital transport, the urgent movement of a newborn from one hospital to another, typically because the receiving institution can provide a level of neonatal intensive care that the discharging hospital cannot. These transports are among the highest-stakes events in neonatal medicine. A tiny infant, often weighing less than a carton of milk, is placed in a portable incubator, connected to a transport ventilator, monitored continuously, and driven or flown across traffic and distance to a destination intensive care unit. Every minute of that journey carries physiologic risk, and the quality of the stabilization before departure can determine whether the infant arrives in stable condition or in crisis.

To isolate the effect of race and ethnicity on transport likelihood, the team calculated odds ratios comparing each racial and ethnic group against non-Hispanic White infants. The comparison groups included non-Hispanic Black infants, infants classified as Asian American, Native Hawaiian, and Pacific Islander, often abbreviated AANHPI, and Hispanic infants. Critically, the models did not stop at this simple comparison. The investigators controlled for a battery of confounding factors organized into four domains: the characteristics of the hospital network in which the birth occurred, hospital-level factors such as the level of the neonatal intensive care unit, maternal sociodemographic characteristics, and infant clinical characteristics that reflect how sick the baby was at the time a transport decision would be made.

The central finding was striking in its specificity. Asian American, Native Hawaiian, and Pacific Islander infants were significantly less likely to be acutely transported than non-Hispanic White infants, with an odds ratio of 0.85 and a p-value of 0.01 after full risk adjustment. An odds ratio of 0.85 translates to roughly a 15 percent lower odds of transport for this group compared with their White counterparts, once all measured sources of confounding have been removed from the equation. In other words, this was not a difference explained by where these infants happened to be born, by the capabilities of their birth hospitals, by their gestational age or birth weight, or by the illness severity recorded in their charts. Something in the system itself appeared to be operating differently for these infants.

Equally instructive was what the analysis revealed about the strongest predictors of transport overall. Hospital-level factors, most notably the level of the neonatal intensive care unit at the birth hospital, were the variables most significantly associated with whether a transport occurred. This makes biological and organizational sense. An infant born at a community hospital without a Level III or Level IV neonatal intensive care unit is far more likely to require transfer to a regional center than an infant born already inside such a center. This mechanism is the entire logic of perinatal regionalization, the organized system through which states route high-risk mothers and infants toward hospitals with the resources to care for them. Studies stretching back to the 1980s have consistently demonstrated that very low birth weight infants delivered at appropriate levels of care experience lower mortality, and meta-analyses have confirmed the survival advantage of regionalized systems.

Yet the system does not always function as designed. Prior work by some of the same investigators has documented the phenomenon of deregionalization, in which an increasing share of very low birth weight infants are born at hospitals that lack the highest levels of neonatal capability, eroding the protective effect of the regional model. Other research from the California Perinatal Quality Care Collaborative has shown that racial and ethnic disparities extend deep into the quality of care itself, with infants from minoritized groups receiving care in neonatal intensive care units that systematically deliver lower-quality services, a pattern described as racial segregation and inequality within the neonatal intensive care landscape. The new transport findings fit into this larger mosaic, suggesting that inequities are not confined to what happens inside intensive care units but also shape the very pathways by which infants move between them.

The authors’ interpretation of their findings is deliberately measured. They conclude that the differing likelihood of acute transport by race and ethnicity may reflect underlying inequities and implicit biases in the system of care. This framing is important because it locates the problem not in the decisions of any single clinician but in the accumulated, often invisible patterns of how referrals are initiated, how transport teams are dispatched, and how risk is assessed across different patient populations. Implicit bias in clinical decision-making is well documented across medicine, and neonatal transport involves rapid judgments under time pressure, exactly the conditions in which unexamined assumptions about patients are most likely to influence behavior. Whether the lower transport rate among AANHPI infants reflects under-triage, differences in referral relationships, communication barriers, or other mechanisms is a question the study was not designed to answer, but the statistically robust association demands investigation.

The implications for policy and practice are concrete. Because hospital-level factors dominate the transport equation, strengthening adherence to regionalization principles, ensuring that high-risk deliveries occur at appropriately equipped hospitals, and auditing transport decisions for racial and ethnic equity are all actionable levers. The study also underscores the value of the granular data infrastructure maintained by quality collaboratives, which made it possible to detect a disparity that would be invisible in national aggregates. For the AANHPI category in particular, the finding adds urgency to calls for disaggregated data, since this grouping bundles together populations with widely divergent risk profiles and outcomes. What the study ultimately delivers is a measurable signal that the ambulance is not the same ambulance for every baby, a finding that should resonate far beyond California and into every perinatal system that claims, as its founding promise, that the sickest infants will reach the highest level of care regardless of who they are.

The dataset underpinning the analysis came from the California Perinatal Quality Care Collaborative, a statewide initiative that collects detailed clinical information from neonatal intensive care units across California. Because these records are gathered under a data use agreement rather than released publicly, the authors note that the underlying data are available only upon reasonable request with the collaborative’s permission. This governance model is common among quality collaboratives, which balance the research value of granular clinical data against the privacy protections owed to patients and participating hospitals.

The study’s statistical approach deserves emphasis. By adjusting simultaneously for network, hospital, maternal, and infant characteristics, the investigators sought to ensure that the observed difference in transport odds was not an artifact of clustering, since infants born at the same hospital share equipment, staffing, and referral practices. This kind of multilevel risk adjustment is essential in perinatal research, where the hospital an infant is born in is itself shaped by maternal residence, insurance, and patterns of segregation that precede any clinical decision.

The findings also connect to a long line of evidence on neonatal outcomes by race and ethnicity. Prior studies have documented disparities in very preterm neonatal morbidities, differences in mortality among very preterm infants across hospitals in large cities, and variation in outcomes for infants born at less than 30 weeks of gestation over time. Systematic reviews of neonatal intensive care have catalogued racial and ethnic differences spanning access, quality, and outcomes, indicating that no single point in the care pathway is immune.

Acute transport occupies a distinctive position in this pathway because it sits at the junction of multiple institutions. A transport decision requires coordination between the referring hospital, the transport team, and the receiving center, each with its own protocols and thresholds for escalation. Disparities arising at this junction may be harder to detect than disparities within a single unit, which makes the statistical signal reported here particularly valuable for quality improvement efforts aimed at ensuring equitable access to regionalized care.

Subject of Research: Racial and ethnic disparities in acute inter-hospital neonatal transport among very low birth weight infants in California

Article Title: Differential transport patterns by race and ethnicity in very low birth weight infants

Article References: Kunz, S. N., Zitnik, M., Helkey, D., Razdan, S., Gould, J. B., Profit, J., & Zupancic, J. A. F. (2026). Differential transport patterns by race and ethnicity in very low birth weight infants. Journal of Perinatology. https://doi.org/10.1038/s41372-026-02896-3

Image Credits: AI Generated

DOI: 10.1038/s41372-026-02896-3

Keywords: very low birth weight, neonatal transport, race and ethnicity, health disparities, neonatal intensive care, perinatal regionalization, odds ratio, California, Journal of Perinatology, AANHPI, NICU level, implicit bias