The biological characteristics of newborns further complicate management. The neonatal immune system is not yet fully developed, so once sepsis occurs, infants are prone to rapid progression toward septic shock and multiple organ dysfunction syndrome. At the same time, the metabolic and enzyme systems of the liver and kidneys remain immature, limiting the ability to clear drugs. Antibiotics routinely used in adults, such as fluoroquinolones and sulfonamides, cannot be directly administered to neonates. Against this backdrop, researchers have increasingly focused on adjunctive therapies built upon standard antibiotic treatment, and plasma transfusion has emerged as one of the most debated candidates. Yet the timing and precise indications for plasma transfusion in neonates remain deeply controversial, prompting a new editorial in the World Journal of Pediatrics by Fang-Rui Ding and Xiao-Yan Li that systematically examines the theoretical foundation, risks, and current clinical application of this approach.

The rationale for using plasma transfusion in sepsis originated in trauma care. Trauma and sepsis share a striking degree of pathophysiological similarity. Both conditions trigger acute intravascular volume depletion and tissue hypoperfusion, as systemic vasodilation and elevated vascular permeability drive massive fluid extravasation, destabilizing the circulation and rapidly progressing to shock. Both disorders also induce severe coagulopathy, marked by excessive consumption of coagulation factors, disrupted anticoagulant pathways, and dysregulated fibrinolysis. Given these overlapping mechanisms, and given that multiple studies have demonstrated that early and active plasma transfusion in trauma patients significantly improves survival and clinical outcomes, it is biologically plausible to infer that plasma might confer comparable benefits in sepsis. This reasoning has shaped clinical intuition for decades, even in the absence of direct evidence in septic patients.

Neonates, especially preterm infants, have inherently low levels of coagulation factors, insufficient immunoglobulins and complement, and a fragile vascular endothelial barrier. When sepsis strikes, the systemic inflammatory response further consumes immune and coagulation-related mediators, worsening disease progression. In theory, plasma transfusion could rapidly replenish these deficient bioactive substances. Immunoglobulin supplementation could strengthen specific immune defenses against pathogens, neutralize toxins, and facilitate infection control. Coagulation factors and fibronectin could optimize hemostasis, preventing and treating sepsis-associated coagulopathy. Complement components could boost bacteriolytic and opsonizing capacity, promoting pathogen clearance. Colloid supplementation might also help maintain blood volume and plasma osmotic pressure, improving tissue perfusion and correcting septic shock. These mechanisms form a coherent and appealing therapeutic hypothesis.

Animal studies have lent support to these theoretical inferences. In a septic rat model, Chang and colleagues found that plasma transfusion raised the 48-hour survival rate from 14 percent to 57 percent compared with normal saline resuscitation. In foals, McTaggart and colleagues demonstrated that plasma transfusion elevated serum immunoglobulin G levels in both healthy and septic animals, and although it exerted no benefit on neutrophil function in healthy foals, it significantly improved neutrophil activity in septic ones. More strikingly, Pereira and colleagues studied neonatal puppies with sepsis and found that combined treatment with plasma and antibiotics improved immune and metabolic parameters, including blood glucose, white blood cell counts, and IgM levels, within 24 hours, shortened recovery of leukocyte indices, reduced lactate levels, and resulted in zero mortality, compared with a 22 percent mortality rate in the antibiotic-only group. Despite these encouraging results, the editorial’s authors caution that no high-grade human evidence has confirmed clinical efficacy, and findings from animal models may not be directly applicable to human neonates because of inherent species and environmental differences.

In humans, the picture grows considerably murkier. Clinical studies of plasma transfusion in sepsis have produced conflicting results, and some have associated transfusion with increased incidence of complications and poorer prognosis. Qin and colleagues, analyzing data from the Medical Information Mart for Intensive Care III database, found that both 28-day and 90-day mortality were significantly higher in the plasma transfusion group than in the non-transfusion group, and plasma transfusion did not improve prognosis even among sepsis patients with coagulopathy, regardless of coagulation state. In a pediatric study by Duan and colleagues involving 262 children with sepsis, 28-day mortality, in-hospital mortality, and multiple organ dysfunction syndrome morbidity were all significantly higher in the plasma transfusion group. Plasma transfusion demonstrated no benefit and was instead significantly associated with an increased risk of adverse outcomes, findings that directly challenge the intuitive appeal of the therapy.

Beyond questions of efficacy, plasma transfusion carries substantial safety risks. Allergic reactions occur at an approximate incidence of 1 to 3 percent. Transfusion-related acute lung injury, or TRALI, has an estimated incidence of 0.08 to 15.1 percent in critically ill patients and accounts for 34 percent of transfusion-related fatalities, although improved mechanistic understanding and donor selection have reduced risks in recent years. Transfusion-associated circulatory overload, or TACO, occurs in roughly 1 percent of transfusions overall but reaches 3.6 to 5.8 percent in critically ill patients, with widespread underdiagnosis and underreporting. While donor screening and pathogen inactivation have substantially reduced infection transmission, residual risks persist, with HIV and hepatitis C transmission rates of approximately 0.02 per 10,000 transfusions, and newly emerging pathogens remain a potential threat. Plasma transfusion may also increase nosocomial infection risk through transfusion-related immunomodulation, a phenomenon linked to postoperative infection in critically ill patients.

Current practice reveals a striking gap between guidelines and reality. Plasma transfusion is relatively common in neonatal intensive care units, with use varying dramatically across centers from 0.17 percent to 8.2 percent, and rates are generally higher for surgical cases and extremely preterm neonates. International guidelines are consistent in their core recommendation: plasma should be given only for active bleeding accompanied by coagulation disorders, and prophylactic transfusion is not recommended. No current sepsis guideline recommends plasma for sepsis itself. Yet observational surveys consistently reveal widespread non-adherence. In European countries, only 29.4 percent of plasma transfusions were given for bleeding, while in South Africa 75 percent of transfusions complied with national guidelines. The authors attribute this deviation to two interrelated factors: the lack of effective targeted interventions for neonatal septic shock, which drives clinicians to adopt plasma as a salvage therapy out of clinical urgency, and the extrapolation of trauma resuscitation experience combined with assumptions about neonatal immune and coagulation immaturity.

The limited human studies specific to neonatal sepsis offer mixed signals. A 1994 study by Acunas and colleagues involving 67 infected neonates found that while intravenous immunoglobulin exerted prominent immune-enhancing effects, plasma transfusion failed to elevate key anti-infective IgG or alter inflammatory markers such as C-reactive protein and fibronectin, indicating no clinical benefit. Conversely, a Nigerian retrospective study by Ogunlesi and colleagues in neonatal tetanus with suspected sepsis observed lower mortality in plasma-transfused neonates, though the difference was statistically insignificant due to small sample size, and all blood culture-positive patients in the transfusion group survived. Eisenfeld and colleagues further demonstrated that plasma transfusion significantly improved neutrophil chemotactic function in critically ill neonates with suspected severe sepsis. Data from other neonatal contexts add further complexity, with studies linking plasma transfusion to retinopathy of prematurity, bronchopulmonary dysplasia, hemodynamically significant patent ductus arteriosus, and necrotizing enterocolitis, though results remain contradictory and appear to depend heavily on transfusion timing, indication, and patient characteristics.

The editorial concludes that there are no definitive evidence-based data confirming that plasma transfusion benefits neonatal sepsis, but this does not mean benefits are absent. The authors call for large-sample, multicenter retrospective and prospective randomized controlled trials with carefully defined inclusion criteria, appropriate coagulation and infection outcomes, and stratified analysis by gestational age and weight to enable individualized treatment. They also urge deeper mechanistic research into the roles of immunoglobulins, coagulation factors, complements, and fibronectin in plasma, alongside safety studies addressing both short-term risks such as TACO, viral transmission, and allergic reactions, and long-term neonatal complications. Until such evidence arrives, plasma transfusion in neonatal sepsis remains a therapy caught between biological plausibility and clinical uncertainty, a gap that only rigorous research can close.

Subject of Research: The use of plasma transfusion as an adjunctive therapy for neonatal sepsis, including its theoretical benefits, clinical evidence, safety risks, and guideline recommendations.

Article Title: Plasma transfusion in neonatal sepsis

Article References: Ding, F.-R., & Li, X.-Y. (2026). Plasma transfusion in neonatal sepsis. World Journal of Pediatrics. https://doi.org/10.1007/s12519-026-01095-6

Image Credits: AI Generated

DOI: 10.1007/s12519-026-01095-6

Keywords: neonatal sepsis, plasma transfusion, fresh frozen plasma, neonatal intensive care, coagulopathy, septic shock, transfusion-related acute lung injury, immunoglobulins, randomized controlled trials, preterm infants, transfusion safety, clinical guidelines

Late-preterm infants are generally born between 34 weeks and 36 weeks and six days of gestation. They are not as immature as babies born at much earlier gestations, but their lungs, nervous systems, immune defenses and metabolic control are still developing. Small-for-gestational-age infants, meanwhile, are smaller than expected for their gestational age, usually defined by a birth weight below the 10th percentile for a population-based reference. Some are constitutionally small but healthy; others have fetal growth restriction, a pathological condition in which the placenta or another maternal-fetal problem limits the delivery of oxygen and nutrients. The distinction is clinically crucial, yet it is not always easy to make at birth.

The central concern is that prematurity and impaired growth may place pressure on different physiological systems at the same time. A late-preterm infant may struggle to maintain body temperature, regulate blood glucose or coordinate sucking, swallowing and breathing. An infant affected by growth restriction may have reduced energy reserves, altered blood-vessel development and evidence of adaptation to a low-oxygen environment before birth. When these conditions coexist, the newborn may have less capacity to compensate for the challenges of early delivery. A baby who is both developmentally immature and nutritionally vulnerable could therefore require closer observation than birth weight or gestational age alone would suggest.

One of the most immediate risks is respiratory instability. Although surfactant production—the process that helps keep the tiny air sacs of the lungs open—improves rapidly during the final weeks of pregnancy, late-preterm lungs can still be less efficient than those of full-term newborns. Growth-restricted fetuses may also experience placental insufficiency, which can affect lung development and oxygen delivery. Together, these factors may increase the likelihood of breathing difficulties, oxygen supplementation or admission to a neonatal unit. Respiratory problems can in turn interfere with feeding, increase energy expenditure and make it harder for the infant to maintain stable blood chemistry.

Metabolic adaptation is another major concern. After the umbilical cord is cut, a newborn must rapidly shift from a continuous placental supply of glucose to an intermittent feeding-based energy system. Smaller infants have limited glycogen and fat stores, while late-preterm infants may not feed effectively because the neurological coordination required for safe oral feeding is still maturing. This combination can increase vulnerability to hypoglycaemia, in which blood glucose falls below the level needed by the brain and other organs. Without early detection and treatment, significant or prolonged hypoglycaemia can become a serious medical emergency, which is why at-risk babies are commonly monitored through repeated glucose measurements.

Temperature regulation presents a similar challenge. Newborns lose heat quickly because they have a large surface area relative to their body mass and limited ability to generate warmth through shivering. Small-for-gestational-age infants generally have less insulating fat, while late-preterm infants may have immature mechanisms for conserving heat. Hypothermia raises oxygen and glucose consumption, potentially creating a damaging cycle in which the infant burns scarce energy reserves simply to remain warm. The resulting metabolic stress may worsen feeding difficulties and respiratory instability, making routine care—skin-to-skin contact, thermal protection and timely feeding—an important part of risk reduction.

The longer-term implications are more complex and cannot be inferred from size or gestational age alone. Early growth restriction has been associated in many studies with changes in vascular biology, insulin sensitivity and later cardiometabolic health, although individual outcomes vary widely. Premature birth can affect neurodevelopment through altered brain maturation, neonatal illness and interruptions to normal sensory and nutritional experiences. When prematurity and restricted growth occur together, researchers are interested in whether their effects are merely additive or whether they interact, producing a risk greater than either exposure would create independently. That is the meaning behind the article’s provocative “double the risk?” framing, although the precise magnitude of risk must come from the underlying data and clinical context.

The causes of this overlap also matter. Late-preterm delivery may be spontaneous, follow premature rupture of the membranes or result from medical decisions made because continuing the pregnancy appears unsafe. Fetal growth restriction can arise from placental dysfunction, maternal hypertension, pre-eclampsia, infection, smoking, nutritional problems or fetal conditions. In some pregnancies, the same placental disease may contribute both to poor fetal growth and to an early delivery. This creates a challenge for researchers: an apparent association between the combined condition and poor outcomes may reflect not only gestational age and birth size, but also the underlying disease that led to delivery. Reliable studies must therefore account for factors such as maternal health, severity of growth restriction, sex, socioeconomic conditions and neonatal treatment.

For clinicians, the message is not that every late-preterm or small newborn will experience serious complications. Most infants in these groups do well, particularly when their needs are recognised early. The concern is that conventional labels can underestimate vulnerability when used in isolation. A late-preterm baby whose weight is also below the expected range may benefit from a more deliberate assessment of breathing, temperature, glucose control, feeding coordination and placental history. Care teams may need to decide carefully whether discharge is safe, since feeding and temperature problems can become apparent only after several hours. Parents may also need clear guidance on warning signs, feeding frequency and when urgent medical advice is required.

The report arrives at a time when neonatal medicine is increasingly focused on precision risk assessment rather than broad categories. Birth weight, gestational age, antenatal Doppler measurements, placental findings and early physiological observations could eventually be combined to identify infants who need additional monitoring while avoiding unnecessary intervention for those at low risk. The question posed by Greenough, Jenkinson and Hickey highlights why this approach matters: two apparently moderate risk factors may become more important when they appear together. As researchers continue to examine the interaction between early birth and restricted growth, the goal will be to translate that knowledge into safer delivery decisions, better newborn surveillance and support that protects vulnerable infants during the critical transition from womb to world.

Subject of Research: The combined health risks associated with late-preterm birth and being small for gestational age.

Article Title: Late preterm and small for gestational age – double the risk?

Article References: Greenough, A., Jenkinson, A. & Hickey, A. “Late preterm and small for gestational age – double the risk?” Pediatr Res (2026). https://doi.org/10.1038/s41390-026-05367-9

Image Credits: AI Generated

DOI: https://doi.org/10.1038/s41390-026-05367-9

Keywords: late preterm birth, small for gestational age, fetal growth restriction, neonatal health, hypoglycaemia, respiratory complications, newborn care, prematurity, placental insufficiency

Healthcare practitioners and researchers have long understood that the initial colonization of the human body by microorganisms is a vital process that can significantly influence future health outcomes. For preterm infants, this process is fraught with challenges, as their immature immune systems place them at a higher risk of infection and chronic diseases. By exploring the bacterial colonization in the upper airways of these infants, researchers aim to uncover potential therapeutic targets that could improve their health prospects.

In this innovative study published in Scientific Reports, a team of scientists embarked on a mission to track the bacterial colonization patterns of preterm infants with very low birth weights. The researchers meticulously collected samples from the upper airways of these infants at different time points, enabling them to construct a comprehensive timeline of microbial colonization. By employing advanced sequencing technologies, they gained unprecedented insights into the microbial diversity residing within the airways of these vulnerable patients.

BPD, a serious lung condition that affects many preterm infants, complicates their clinical management. The disease is characterized by inflammation and scarring of the lungs and is linked to the mechanical ventilation and oxygen therapy often required to support these infants. Understanding the microbiome’s role in BPD is crucial as it may influence the pathophysiology of the disease. The bacterial populations residing in the upper airways may interact with local immune responses, potentially exacerbating or alleviating inflammation.

The findings from this research reveal that bacterial colonization begins early in life, even within the first few days after birth. The study identified a diverse array of bacterial species, some of which are known to be pivotal in maintaining respiratory health. Conversely, there was also a notable presence of pathogenic bacteria, raising questions about their role in the development or exacerbation of BPD. Through rigorous analysis, the researchers uncovered that specific bacterial communities appeared to flourish in infants with BPD compared to their healthier counterparts.

Interestingly, the dynamic nature of bacterial colonization suggests that these microbial communities are not static. Instead, they undergo rapid changes in response to the infant’s health status, environmental factors, and medical interventions. The researchers emphasized the need for continuous monitoring of these microbial populations as they may serve as indicators of respiratory health or disease progression in preterm infants.

This research also aligns with the growing body of literature advocating for the prebiotic and probiotic interventions in neonatal care. By understanding the bacterial landscape of the upper airway, potential strategies could be devised to manipulate these communities favorably. For instance, could the administration of specific probiotics during the neonatal period enhance microbial diversity and suppress pathogenic growth? This question represents an exciting frontier for future research.

The implications of this study extend beyond immediate clinical applications. Bacterial colonization patterns can provide insights into the broader understanding of how infants adapt to the challenges of life outside the womb. Each exposure and subsequent colonization event can shape the infant’s immune responses and metabolic pathways, laying the groundwork for their long-term health. By prioritizing research in this area, the scientific community can strive towards more holistic approaches to neonatal care.

Moreover, the methodology employed in this work sets a precedent for future investigations. The use of metagenomic sequencing not only captures the richness of microbial diversity but also reveals the potential interactions between different species. This brings to light the significance of microbial networks and their collective impact on health. The lessons learned from studying preterm infants may ultimately translate into broader advancements in our understanding of microbiomes across different populations.

As awareness grows about the relevance of the microbiome in various health contexts, this study serves as a pivotal reminder of the delicate balancing act that occurs in the early life stages of infants. Realizing how early interventions can steer the establishment of a healthy microbiome will be crucial in developing targeted therapies for at-risk populations.

In summary, Frodermann and colleagues have made significant strides in opening the dialogue around microbial colonization in preterm infants. The study prompts essential questions about potential interventions to manipulate and improve these bacterial communities for better health outcomes. The researchers advocate for continued exploration of the upper airway microbiome, given its potential to inform clinical strategies aimed at preventing or mitigating developmental issues, including chronic lung diseases like BPD.

Ultimately, this research underscores the imperative of interdisciplinary collaboration in neonatal care, integrating microbiology, immunology, and clinical medicine to foster environments that optimize outcomes for our most vulnerable patients. As we continue to unravel the complexities of the human microbiome, the hope is that this knowledge will lead to tangible improvements in the care and quality of life for preterm infants around the globe.

Subject of Research: Dynamics of postnatal upper airway bacteria colonization in preterm infants <1000g and bronchopulmonary dysplasia.

Article Title: Dynamics of postnatal upper airway bacteria colonization in preterm infants <1000g and bronchopulmonary dysplasia.

Article References:

Frodermann, T., Rochwalsky, U., Selting, A. et al. Dynamics of postnatal upper airway bacteria colonization in preterm infants <1000g and bronchopulmonary dysplasia.
Sci Rep (2025). https://doi.org/10.1038/s41598-025-29038-7

Image Credits: AI Generated

DOI: 10.1038/s41598-025-29038-7

Keywords: Microbiome, Bacterial colonization, Preterm infants, Bronchopulmonary dysplasia, Respiratory health, Metagenomic sequencing, Neonatal care.