Serdar Beken

Objective Late-onset sepsis (LOS) remains a major cause of neonatal mortality, yet accurate endpoints to monitor recovery are lacking. Though clinical cure is commonly used as a core outcome in trials, no consensus definition exists. This study aimed to develop a clinical cure score to monitor recovery in neonatal LOS. Design A multidisciplinary expert panel reached consensus on items using a modified Delphi approach (development phase). Content validity was quantified using the Content Validity Index (CVI). Face validity was assessed through end-user surveys evaluating comprehensibility and user-friendliness. Inter-rater/intrarater reliability was examined by having end-users score six video-fragments twice (evaluation phase). Intraclass correlation coefficients (ICCs) were calculated. A prospective pilot study compared scores between sepsis and control patients to propose a clinical cure cut-off (validation phase). Results Nine experts needed seven surveys and nine meetings to reach predefined CVI targets. 87 end-users completed the face validity survey, rating comprehensibility and user-friendliness 4.4/5. The final score comprised nine clinical items, with maximum scores of 24 (ventilated) and 27 (non-ventilated), following a ‘back-to-baseline’ concept. Inter-rater ICCs were 0.68 (absolute agreement) and 0.75 (consistency) among 52 raters. Intrarater ICC was 0.83 (31 raters). 15 sepsis and 17 control patients were included in the prospective study. Median scores of sepsis patients improved over time until reaching scores of controls. Proposed clinical cure cut-offs were >20 for ventilated and >23 for non-ventilated neonates. Conclusions The Neonatal Recovery Of Sepsis Assessment score provides a promising, user-friendly tool that standardises clinical cure assessment in research and may support future clinical follow-up of LOS neonates.

Background/Objectives: Intrahepatic cholestasis of pregnancy (ICP) is associated with adverse perinatal outcomes. However, its metabolic consequences on newborns remain inadequately characterized. This study investigated amino acid, carnitine, and acylcarnitine profiles in neonates born to mothers with ICP. Methods: This retrospective study encompassed 299 neonates born to mothers with ICP. For comparative analysis, term infants without additional complications (ICP-term, n = 150) were compared with term controls (n = 150). Capillary blood samples collected at 24–48 h of life as part of newborn screening were analyzed using LC–MS/MS for acylcarnitine and amino acid profiles. Results: The ICP cohort exhibited a high preterm delivery rate (46.2%), with maternal bile acids negatively correlating with gestational age (r = −0.266, p < 0.001). No inborn errors of metabolism were observed. Elevated levels of amino acids (alanine, leucine/isoleucine, valine, tyrosine, arginine, glycine, and ornithine) and specific acylcarnitines (C5, C5-OH, C10:1, and C18:2), along with decreased levels of amino acids (argininosuccinic acid and glutamic acid) and specific acylcarnitines (C3, C5-DC, C6-DC, C14, C14:1, C16, C16:1, and C18:1-OH), were observed in ICP-term neonates (p < 0.05). Receiver operating characteristic curve analysis identified ornithine (area under the curve [AUC] = 0.74) and leucine/isoleucine (AUC = 0.73) as strong discriminators. A multivariable model integrating multiple metabolites achieved high accuracy (AUC = 0.86 ± 0.03). Conclusions: This first comprehensive characterization of neonatal metabolic alterations in ICP reveals amino acid metabolism, fatty acid oxidation, and mitochondrial function disruptions, suggesting fetal adaptation to a cholestatic intrauterine environment. Metabolomic profiling may improve understanding of maternal–fetal interactions and inform strategies for risk stratification and long-term monitoring.

To investigate early metabolic biomarkers in neonates born to mothers with gestational diabetes mellitus (GDM), focusing on amino acid and acylcarnitine profiles to assess metabolic risk, including obesity and future metabolic syndrome. This retrospective study analyzed dried blood spot samples from 184 GDM and 167 control neonates. GDM was categorized as large-for-gestational-age (LGA) or appropriate-for-gestational-age (AGA). Amino acid and acylcarnitine concentrations at 24-48 h postnatal age were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Neonatal hypoglycemia was defined and managed according to standard guidelines. Principal component analysis (PCA) was performed to identify clustering patterns. Tyrosine concentrations were significantly lower in the GDM-LGA group compared to the control-AGA group (p = 0.018). Total carnitine levels were higher in GDM-LGA infants relative to controls (p < 0.05), reflecting increased fatty acid mobilization in larger infants. Specific long-chain acylcarnitines, such as C18:1 and C18:2, were lower in GDM group. whereas stearoyl carnitine (C18:0) was elevated, indicating an altered fatty acid oxidation profile. PCA revealed distinct metabolic patterns, suggesting early metabolic heterogeneity in GDM. The study identifies distinctive early metabolic profiles in neonates of gestational diabetic mothers, including lower tyrosine and altered acylcarnitine patterns, which may signal a predisposition to metabolic disorders. These findings support early metabolic screening protocols and targeted follow-up for high-risk infants. Longitudinal studies are warranted to confirm the predictive value of these biomarkers and to clarify the long-term impacts of metabolic disturbances in GDMs.

Background: While parent-delivered pain management has been demonstrated to effectively reduce neonatal procedural pain responses, little is known about to what extent it is utilized. Our aim was to explore the utilization of parents in neonatal pain management and investigate whether local guidelines promote parent-delivered interventions. Methods: A web-based survey was distributed to neonatal units worldwide. Results: The majority of the 303 responding neonatal intensive care units (NICUs) from 44 countries were situated in high-income countries from Europe and Central Asia. Of the responding units, 67% had local guidelines about neonatal pain management, and of these, 40% answered that parental involvement was recommended, 27% answered that the role of parents in pain management was mentioned as optional, and 32% responded that it was not mentioned in the guidelines. According to the free-text responses, parent-delivered interventions of skin-to-skin contact, breastfeeding, and parental live singing were the most frequently performed in the NICUs. Of the responding units, 65% answered that parents performed some form of pain management regularly or always. Conclusions: There appears to be some practice uptake of parent-delivered pain management to reduce neonatal pain in high-income countries. Additional incorporation of these interventions into NICU pain guidelines is needed, as well as a better understanding of the use of parent-delivered pain management in low- and middle-income countries.

The incidence of invasive candidiasis (IC) in neonatal intensive care units (NICUs) has significantly increased. Although C. albicans is still the most common pathogen detected in IC cases (60-75%), the increase in the use of prophylactic antifungal therapies and empirical echinocandin has led to a shift in detected pathogens to non-albicans candida species such as C. glabrata (2-8%). In the past, C. glabrata was considered one of the relatively non-pathogenic saprophytes of the normal flora. However, mucosal and systemic C. glabrata infections have escalated with the increase in the survival rates of premature newborns, prolonged hospitalization, and the widespread use of immunosuppressives and broad-spectrum antibiotics and started to appear more frequently as an important nosocomial pathogen, especially with its natural resistance to the azole antifungals. In this article, we aimed to draw attention to the importance of C. glabrata in NICUs by presenting extremely low-birth-weight premature twins with severe clinical course.

Introduction:Restricted or enhanced intrauterine growth is associated with elevated risks of early and late metabolic problems in humans. Metabolomics based on amino acid and carnitine/acylcarnitine profile may have a role in fetal and early postnatal energy metabolism. In this study, the relationship between intrauterine growth status and early metabolomics profile was evaluated.Materials and Methods:A single-center retrospective cohort study was conducted. Three hundred and sixty-one newborn infants were enrolled into the study, and they were grouped according to their birth weight percentile as small for gestational age (SGA,n= 69), appropriate for gestational age (AGA,n= 168), and large for gestational age (LGA,n= 124) infants. In all infants, amino acid and carnitine/acylcarnitine profiles with liquid chromatography-tandem mass spectrometry (LC-MS/MS) were recorded and compared between groups.Results:LGA infants had higher levels of glutamic acid and lower levels of ornithine, alanine, and glycine (p< 0.05) when compared with AGA infants. SGA infants had higher levels of alanine and glycine levels when compared with AGA and LGA infants. Total carnitine, C0, C2, C4, C5, C10:1, C18:1, C18:2, C14-OH, and C18:2-OH levels were significantly higher and C3 and C6-DC levels were lower in SGA infants (p< 0.05). LGA infants had higher C3 and C5:1 levels and lower C18:2 and C16:1-OH levels (p< 0.05). There were positive correlations between free carnitine and phenylalanine, arginine, methionine, alanine, and glycine levels (p< 0.05). Also, a positive correlation between ponderal index and C3, C5-DC, C14, and C14:1 and a negative correlation between ponderal index and ornithine, alanine, glycine, C16:1-OH, and C18:2 were shown.Conclusion:We demonstrated differences in metabolomics possibly reflecting the energy metabolism in newborn infants with intrauterine growth problems in the early postnatal period. These differences might be the footprints of metabolic disturbances in future adulthood.

We have read the paper by Leung 'The younger the milder clinical course of COVID‐19: Even in newborns?' with interest.¹ In the article, it was emphasized a severe disease course in neonates compared to the pediatric age group (1 months‐ 2 years of age) and possible mechanisms for severity in neonatal paeriod was discussed. As the number of people affected by this new coronavirus (SARS‐CoV‐2) infections, higher number of newborns have been reported.

Background Acute kidney injury (AKI) is a common complication of congenital heart diseases (CHDs) after cardiac surgery. This study aimed to define the frequency and critical course, risk factors and short-term outcomes of AKI in postoperative CHD neonates. Methods Postoperatively followed term CHD newborn infants were enrolled in the study. Infants with congenital anomalies of the urinary tract and other major congenital anomalies were excluded. Neonatal modified KDIGO criteria were used to assess AKI. Results A total of 199 postoperatively followed newborn infants were included in the study. Acute kidney injury was detected in 71 (35.6%) patients. Of these patients, 24 (33.8%) were in stage 1, 14 (19.7%) in stage 2, and 33 (46.5%) in stage 3. Acute kidney injury occurred within the first week (median 1 day [IQR 1–2 days]) of cardiac surgery in 93% of the patients. The duration of invasive respiratory support and extracorporeal membrane oxygenation (ECMO) and mortality were significantly higher in stage 3 patients. Higher vasoactive-inotropic score (OR, 1.02; 95% CI, 1.0–1.04; p = 0.008) and receiving ECMO (OR, 7.9; 95% CI, 2.6–24.4; p = 0.001) were associated with risk for the development of AKI. The mortality rate was 52.1% in the AKI (+) patients, and having AKI (OR 7.1; 95% CI, 3.5–14.18) was significantly associated with mortality. Conclusion Acute kidney injury, a common early complication after critical neonatal CHD cardiac surgery, is associated with increased morbidity and mortality. Stage 3 AKI is associated with significantly higher mortality rates. Graphical Abstract