In the intricate and profoundly delicate realm of neonatal care, infants born before the threshold of 24 weeks’ gestation represent an extraordinary challenge to contemporary medicine. Their survival, although increasingly possible through advances in perinatal and neonatal intensive care, involves navigating a precarious landscape of physiological immaturity and vulnerability to life-threatening complications. Among these, bacterial and fungal infections stand out as predominant threats that critically influence morbidity and mortality rates. A recent comprehensive review published in the Journal of Perinatology sheds pivotal light on these infectious threats, offering valuable insights into their nature, incidence, and the clinical conundrums they present.
Premature infants born before 24 weeks represent a unique cohort characterized by underdeveloped immune systems, immature skin and mucosal barriers, and nascent organ functionality. These physiological weaknesses collectively predispose the neonate to invasive infections by opportunistic pathogens. The review meticulously delineates the microbial spectrum, highlighting both bacterial and fungal pathogens that commonly afflict this vulnerable population. Key pathogens include coagulase-negative staphylococci, gram-negative bacteria, and Candida species, which frequently invade through central lines or disrupted skin integrity.
The neonatal immune system at this gestational age is markedly underdeveloped, lacking the robust innate and adaptive responses seen in more mature infants. Neutrophil functionality, including chemotaxis and phagocytosis, is impaired, while the production of antimicrobial peptides is deficient. Furthermore, the humoral immune system is immature, with low levels of maternal immunoglobulin G (IgG) transfer, making these infants particularly susceptible to systemic infections that can rapidly escalate. This immunological landscape necessitates heightened vigilance and tailored antimicrobial strategies in clinical practice.
In parallel with immunological immaturity, external factors significantly compound infection risks. The necessity of intensive invasive procedures, including mechanical ventilation, central venous access, parenteral nutrition, and prolonged hospital stays, provide portals of entry and conducive environments for pathogen proliferation. Central line-associated bloodstream infections (CLABSIs) remain among the leading contributors to morbidity. The intricate balance between life-sustaining interventions and the inadvertent facilitation of infections encapsulates a profound therapeutic dilemma.
The review underscores the dual challenge of accurate diagnosis and timely therapeutic intervention. Neonatal sepsis in infants below 24 weeks gestation often presents with nonspecific clinical signs, complicating early recognition. Conventional diagnostic markers, such as C-reactive protein (CRP) and procalcitonin, show limited sensitivity and specificity in this population due to their immature inflammatory responses. Consequently, clinicians often rely on a comprehensive assessment incorporating clinical evaluation, laboratory markers, and microbiological cultures, despite their inherent limitations.
Antimicrobial stewardship emerges as an essential theme, balancing the imperatives of prompt empirical treatment against risks of antimicrobial resistance and microbiome disruption. Overuse of broad-spectrum antibiotics can foster resistant organisms and alter the delicate balance of neonatal gut flora, with potential long-term health consequences including necrotizing enterocolitis (NEC). The review advocates for judicious use of antimicrobials, guided by local microbiological epidemiology, and emphasizes the importance of narrow-spectrum agents when pathogen identification permits.
Fungal infections, primarily candidemia, represent a significant concern given their association with high mortality rates in extremely preterm infants. Candida albicans, along with emerging non-albicans species, frequently colonizes mucosal surfaces and enters the bloodstream, particularly in the context of compromised immune defenses and intravenous catheterization. The review accentuates the necessity of antifungal prophylaxis in high-risk cohorts, although the selection of agents must weigh efficacy against toxicity in this fragile population.
Further complicating the management of fungal infections are the diagnostic difficulties due to low sensitivity of blood cultures for fungi and the subtle clinical presentation. Advanced molecular diagnostics, including polymerase chain reaction (PCR) techniques and biomarkers such as β-D-glucan, are promising adjuncts for early detection but require further validation within this specific neonatal subset. Integration of these modalities into routine clinical practice could revolutionize infection control.
The review also delineates the overarching implications of infection on long-term neurodevelopmental outcomes. Systemic infections during this critical developmental window have been associated with adverse neurologic sequelae, including cerebral palsy, cognitive impairments, and sensory deficits. The pathophysiology intertwines direct infectious injury with inflammatory cascades, articulating the necessity of preventive strategies extending beyond the acute neonatology setting.
In terms of prevention, stringent infection control protocols in neonatal intensive care units (NICUs) are paramount. Meticulous hand hygiene, adherence to aseptic technique during invasive procedures, and minimization of indwelling device duration are standard pillars. The review highlights innovative approaches such as antimicrobial-impregnated catheters and the utilization of probiotics as adjunctive measures to enhance host defenses and prevent colonization by pathogenic organisms.
Emerging research avenues illuminated by the review include the exploration of immunomodulatory therapies aimed at bolstering the immature neonatal immune system. Agents such as granulocyte colony-stimulating factor (G-CSF) and intravenous immunoglobulin (IVIG) have been evaluated with mixed results, underscoring the complexity of safely augmenting immunity without exacerbating inflammation. Rigorous randomized controlled trials are essential to clarify their roles.
A further area of evolving interest is the interplay between the neonatal microbiome and infectious risk. Dysbiosis—a disruption of the normal microbial community—has been implicated in susceptibility to infections and other morbidities. The review calls for integrative studies employing metagenomic sequencing to profile microbial communities and identify protective versus pathogenic signatures, aiming to harness microbiome modulation as a preventive strategy.
The relentless advances in neonatal care technology, while driving improved survival rates of extremely premature infants, simultaneously bring new challenges in infection management. The review’s holistic perspective encourages interdisciplinary collaboration among neonatologists, microbiologists, immunologists, and pharmacologists to devise comprehensive frameworks that integrate prevention, early diagnosis, and individualized therapy.
Ultimately, the review by Flannery, Green, Mehler, and colleagues constitutes a landmark synthesis in the field of perinatal infectious diseases, framing current knowledge and illuminating pathways for future investigation. Their meticulous analysis underscores that while the threshold of viability continues to be pushed earlier in gestational age, the accompanying infectious risks demand equal innovation and vigilance.
This comprehensive elucidation resonates powerfully with the neonatal professional community and stakeholders concerned with the fragile beginnings of life. As neonatal survival steadily improves, the imperative to mitigate infectious complications grows ever more critical, promising profound implications for clinical practice and outcomes in this most vulnerable population.
Subject of Research: Bacterial and fungal infections in extremely premature infants born before 24 weeks’ gestation
Article Title: Bacterial and fungal infections in infants born before 24 weeks’ gestation: a review
Article References:
Flannery, D.D., Green, M.B., Mehler, K. et al. Bacterial and fungal infections in infants born before 24 weeks’ gestation: a review. J Perinatol (2026). https://doi.org/10.1038/s41372-026-02562-8
Image Credits: AI Generated
DOI: 10.1038/s41372-026-02562-8
Keywords: Neonatal infections, extremely preterm infants, bacterial pathogens, fungal infections, candidemia, neonatal immunity, antimicrobial stewardship, neonatal intensive care, microbiome, infection prevention
