Plasmatic profiles of cytokines/chemokines, glial fibrillary acidic protein (GFAP) and MRI brain damage in neonates with hypoxic ischemic encephalopathy (HIE).

BACKGROUND: Perinatal hypoxia triggers the release of cytokines and chemokines by neurons, astrocytes and microglia. In response to hypoxia-ischemia resting/ramified microglia proliferate and undergo activation, producing proinflammatory molecules. The brain damage extension seems to be related to both the severity of hypoxia and the balance between pro and anti-inflammatory response and can be explored with neuroimaging. AIMS: The aim of this preliminary study was to explore possible relationships between plasma levels of inflammatory cytokines/chemokines and the severe brain damage detectable by Magnetic Resonance Imaging (MRI), performed during the hospitalization. METHODS: In 10 full terms neonates with hypoxic ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH), divided into cases and controls, according to MRI results, we measured and compared the plasma levels of CCL2/MCP-1, CXCL8, GFAP, IFN y, IL-10, IL-18, IL-6, CCL3, ENOLASE2, GM-CSF, IL-1b, IL-12p70, IL-33, TNFα, collected at four different time points during TH (24, 25-48, 49-72 h of life, and 7-10 days from birth). Five of enrolled babies had pathological brain MRI (cases) and 5 had a normal MRI examination (controls). Cytokines were measured by Magnetic Luminex Assay. MRI images were classified according to Barkovich's score. RESULTS: Mean levels of all cytokines and molecules at time T1 were not significantly different in the two groups. Comparing samples paired by day of collection, the greatest differences between cases and controls were found at times T2 and T3, during TH. At T4, levels tended to get closer again (except for IL-6, IL10 and IL18). Infants with worse MRI showed higher plasmatic GFAP levels than those with normal MRI, while their IL-18 was lower. The mean levels of CCL3MIP1alpha, GMCSF, IL1BETA overlapped throughout the observation period in both groups. CONCLUSION: In a small number of infants with worse brain MRI, we found higher levels of GFAP and of IL-10 at T4 and a trend toward low IL-18 levels than in infants with normal MRI, considered early biomarker of brain damage and a predictor of adverse outcome, respectively. The greatest, although not significant, difference between the levels of molecules was found in cases and controls at time points T2 and T3, during TH.

Assessment of hemodynamic dysfunction in septic newborns by functional echocardiography: a systematic review.

BACKGROUND: Neonatal sepsis remains a leading cause of mortality in neonatal units. Neonatologist-performed echocardiography (NPE) offers the potential for early detection of sepsis-associated cardiovascular dysfunction. This review examines available echocardiographic findings in septic neonates. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically reviewed prospective observational, cross-sectional, case control, and cohort studies on septic newborns with echocardiographic assessments from PubMed, Scopus and Embase. Quality assessment employed the Newcastle-Ottawa Scale, with results analyzed descriptively. RESULTS: From an initial pool of 1663 papers, 12 studies met inclusion criteria after relevance screening and eliminating duplicates/excluded studies. The review encompassed 438 septic newborns and 232 controls. Septic neonates exhibited either increased risk of pulmonary hypertension or left ventricular diastolic dysfunction, and a warm shock physiology characterized by higher cardiac outputs. DISCUSSION: The included studies exhibited heterogeneity in sepsis definitions, sepsis severity scores, echocardiographic evaluations, and demographic data of newborns. Limited sample sizes compromised analytical interpretability. Nonetheless, this work establishes a foundation for future high-quality echocardiographic studies. CONCLUSION: Our review confirms that septic neonates show significant hemodynamic changes that can be identified using NPE. These findings underscore the need for wider NPE use to tailor hemodynamics-based strategies within this population. IMPACT: 1. Our study emphasizes the value of neonatologist-performed echocardiography (NPE) as a feasible tool for identifying significant hemodynamic changes in septic neonates. 2. Our study underscores the importance of standardized echocardiographic protocols and frequent monitoring of cardiac function in septic neonates. 3. The impact of the study lies in its potential to increase researchers' awareness for the need for more high-quality echocardiographic data in future studies. By promoting wider use of NPE, neonatologists can more accurately assess the hemodynamic status of septic newborns and tailor treatment approaches, potentially improving patient outcomes.

Unusual cerebral intraventricular hemorrhage and cardiomyopathy related to congenital cytomegalovirus from non-primary maternal infection: a case report.

BACKGROUND: Congenital cytomegalovirus (cCMV) infection, resulting from non-primary maternal infection or reactivation during pregnancy, can cause serious fetal abnormalities, complications in the immediate neonatal period, and severe sequelae later in childhood. Maternal non-primary cytomegalovirus infection in pregnancy is transmitted to the fetus in 0.5-2% of cases (1). CASE PRESENTATION: An African full term male newbornwas delivered by emergency caesarean section. Due to signs of asphyxia at birth and clinical moderate encephalopathy, he underwent therapeutic hypothermia. Continuous full video-electroencephalography monitoring showed no seizures during the first 72 h, however, soon after rewarming, he presented refractory status epilepticus due to an intracranial hemorrhage, related to severe thrombocytopenia. The patient also presented signs of sepsis (hypotension and signs of reduced perfusions). An echocardiography revealed severe cardiac failure with an ejection fraction of 33% and signs suggestive of cardiomyopathy. Research for CMV DNA Polymerase Chain Reaction (PCR) on urine, blood, cerebrospinal fluid, and nasopharyngeal secretions was positive.The mother had positive CMV IgG with negative IgM shortly before pregnancy. Serology for CMV was therefore not repeated during pregnancy, but CMV DNA performed on the Guthrie bloodspot taken at birth yielded a positive result, confirming the intrauterine transmission and congenital origin of the infection. The baby was discharged in good general condition and follow up showed a normal neurodevelopmental outcome at 9 months. CONCLUSION: Although uncommon, congenital cytomegalovirus infection should be included in the differential diagnosis of intraventricular hemorrhage and cardiomyopathy. Furthermore, this case highlights the possible severity of congenital cytomegalovirus infection, even in cases of previous maternal immunity.

Stop in Time: How to Reduce Unnecessary Antibiotics in Newborns with Late-Onset Sepsis in Neonatal Intensive Care.

The fear of missing sepsis episodes in neonates frequently leads to indiscriminate use of antibiotics, and prescription program optimization is suggested for reducing this inappropriate usage. While different authors have studied how to reduce antibiotic overprescription in the case of early onset sepsis episodes, with different approaches being available, less is known about late-onset sepsis episodes. Biomarkers (such as C-reactive protein, procalcitonin, interleukin-6 and 8, and presepsin) can play a crucial role in the prompt diagnosis of late-onset sepsis, but their role in antimicrobial stewardship should be further studied, given that different factors can influence their levels and newborns can be subjected to prolonged therapy if their levels are expected to return to zero. To date, procalcitonin has the best evidence of performance in this sense, as extrapolated from research on early onset cases, but more studies and protocols for biomarker-guided antibiotic stewardship are needed. Blood cultures (BCs) are considered the gold standard for the diagnosis of sepsis: positive BC rates in neonatal sepsis workups have been reported as low, implying that the majority of treated neonates may receive unneeded drugs. New identification methods can increase the accuracy of BCs and guide antibiotic de-escalation. To date, after 36-48 h, if BCs are negative and the baby is clinically stable, antibiotics should be stopped. In this narrative review, we provide a summary of current knowledge on the optimum approach to reduce antibiotic pressure in late-onset sepsis in neonates.

Role of Brain Elastography in the Neonatal Setting: State of the Art of Ultrasonographic Techniques and Future Perspectives.

Magnetic resonance imaging is currently used in the neonatal setting for assessing features of the neonatal brain. However, its utilization is constrained by logistic, technical, or clinical challenges. Brain elastography is a new research technique which enhances the diagnostic capability of traditional imaging, and can be paired with both ultrasonography and magnetic resonance imaging. In particular, brain elastography adds objective and quantitative information to traditional imaging by detecting differences in tissue elasticity/stiffness, which may represent a surrogate marker of the physiologic and pathologic features of the neonatal brain. To date, very limited experience exists about the use of brain elastography specifically in the neonatal setting. The aim of the present review was to describe the most recent information about the feasibility and diagnostic accuracy of brain ultrasound elastography (USE) in neonates, and to provide information about the possible future applications and perspectives of brain elastography.

Intersociety Position Statement on the Prevention of Ophthalmia Neonatorum in Italy.

There is currently no worldwide agreement on the real need to administer conjunctival antibiotics to neonates at birth to prevent neonatal conjunctivitis (usually defined as ophthalmia neonatorum) by Chlamydia trachomatis and Neisseria gonorrhoeae. Therefore, there is wide variability in antibiotic administration, conditioned mainly by the social and health context. In Italy, a law enacted in 1940 required doctors and midwives to administer ophthalmic prophylaxis with 2% silver nitrate to all newborns at birth. This law was repealed in 1975 and since then there has been no clear guidance on the use of ophthalmia neonatorum prophylaxis at birth. Since neonatal conjunctivitis caused by C. trachomatis and N. gonorrhoeae is not reported, we carried out a nationwide survey of 1,041,384 neonates across all Italian birth centers to evaluate the incidence of ophthalmia neonatorum and the current practice of prophylaxis. After analyzing the results, we formulated an intersociety position statement on the prevention of ophthalmia neonatorum to update and standardize this prevention strategy in Italy.