Jan Janota

Neonatal vitamin B12 (B12) deficiency can cause neurodevelopmental harm, and newborn screening (NBS) may enable early detection and treatment. We conducted a multicenter pilot project in four Prague university hospitals between 1 June 2022 and 30 June 2025. Algorithms included the determination of propionylcarnitine-derived primary markers using flow-injection tandem mass spectrometry and second-tier methylmalonic acid (MMA), with total homocysteine measured only when MMA was increased. Of 34,302 screened newborns with consent, 1365 (3.98%) triggered second-tier testing; 9 had MMA > 2.5 µmol/L, of which 8 met the case definition after confirmatory testing, giving a birth frequency of 1:4228 (95% CI 1:2176–1:9931). Positive predictive value was 0.59% (95% CI 0.25–1.15%) and 88.89% (95% CI 51.75–99.72%) for the primary test and second-tier MMA, respectively, with a false positive rate of 0.00292% (95% CI 0.000074–0.01625%). All affected infants were treated orally with cyanocobalamin. Maternal work-up identified confirmed B12 deficiency in four of eight mothers and premalignant gastric changes in two of four positive women. These data support the feasibility, low cost, and clinical utility of incorporating B12 deficiency into Czech NBS, with benefits extending beyond newborn health.

The endothelium plays a crucial role in maintaining vascular homeostasis. Inflammation is initiated by activation of endothelial cells, which results in endothelial dysfunction. Dysfunction of the endothelium can have significant consequences in neonates and children. It is essential to understand the mechanisms underlying endothelial dysfunction in neonates and paediatric population to develop effective therapy interventions and improve outcomes. The aim of the review is to summarize the recent studies on the endothelium-associated molecules as biomarkers of systemic inflammatory conditions in the neonatal and paediatric population.

Inflammation is considered a fundamental process accompanying physiological human birth, also playing a role in perinatal pathologies. The goal of the study was to assess the concentrations of inflammatory molecules with respect to the mode of delivery and dynamics of inflammatory molecules in neonatal samples in the first 48–72 hours of life. The concentrations of inflammatory cytokines were measured using the Luminex®xMAP multi-analyte profiling platform in cord blood and peripheral neonatal blood. Study groups included newborns delivered spontaneously (spontaneous group) and via elective caesarean section (elective group). Cord blood concentrations of interleukin 6 (IL-6) and procalcitonin were significantly higher (P < 0.0001) in the spontaneous group compared to the elective group. Neonatal blood concentrations of tumour necrosis factor (TNF) from the elective group were significantly higher com­pared to the spontaneous group (P = 0.0077). The concentrations of procalcitonin and TNF significantly increased within the first 48 to 72 hours following either mode of delivery. IL-6 and IL-18 were significantly higher in neonatal compared to umbilical cord blood in the elective group only, while the increase in the spontaneous group did not reach statistical significance. The concentrations of IL-1α, IL-1β, IL-17A and IL-22 did not show significant differen­ces between the spontaneous and elective groups as well as between umbilical cord and neonatal blood. Our findings show physiological differences in the levels of inflammatory molecules following spontaneous vaginal delivery and elective caesarean section. The results can be used as baseline values for the research of various pathologies in newborns.

Objective: Changes in oximeter averaging times have been noted to affect alarm settings. Automated algorithms (A-FiO₂) assess FiO₂ faster than oximeter averaging, potentially impacting their effectiveness.Methods: In a single NICU routinely using 15 fabian-PRICO A-FiO₂ systems, neonates were randomly exposed to SpO₂ averaging time settings switched every 12 h among short (2–4 s), medium (10 s), and long (16 s) oximeter averaging times for the entire duration of their A-FiO₂ exposure. Primary endpoints were the percent time in the set SpO₂ target range (dependent on PMA), SpO₂< 80%, and SpO₂> 98%, excluding FiO₂ = 0.21.Results: Ten VLBW neonates were enrolled over 11 months. At entry, they were 17 days old (IQR: 14–19), with an adjusted gestational age of 29 weeks (IQR: 27–30). The study included data from 272 days of A-FiO₂ control (34% short, 32% medium, and 34% long). Respiratory support was predominantly non-invasive (53% NCPAP, 40% HFNC, and 6% NIPPV). The aggregate SpO₂ exposure levels were 67% (IQR: 55–82) in the target range, 5.4% (IQR: 2.0–10) with SpO₂< 80%, and 1.2% (IQR: 0.4–3.1) with SpO₂> 98%. There were no differences in the target range time between the SpO₂ averaging time settings. There were differences at the SpO₂ extremes (p ≤ 0.001). The medium and long averaging were both lower than the short, with the difference larger than predicted. Multivariate analysis revealed that these findings were independent of subject, ventilation mode, target range, and overall stability.Conclusions: This A-FiO₂ algorithm is effective regardless of the SpO₂ averaging time setting. There is an advantage to the longer settings, which suggest an interaction with the controller.

Objectives: To evaluate the efficacy of presepsin (P-SEP) as a potential biomarker of early-onset neonatal sepsis (EOS) and compare it to other routinely used markers of inflammation. To establish the cut-off values of P-SEP for EOS.Study design: 184 newborns were prospectively recruited between January 2018 to December 2020. Newborns >34th gestational week with suspected infection were included up to 72 h after delivery, and divided into three categories (i.e., unlikely, possible, and probable infection) based on risk factors, clinical symptoms and laboratory results. Values of plasma P-SEP were sequentially analyzed.Results: Median values of P-SEP in newborns with probable infection were significantly higher compared to healthy newborns (p = 0.0000013) and unlikely infection group (p = 0.0000025). The AUC for discriminating the probable infection group from the unlikely infection group was 0.845 (95% Cl: 0.708–0.921). The diagnostic efficacy of P-SEP was highest when used in combination with IL-6 and CRP (0.97; 95% CI: 0.911–0.990). The optimal cut-off value of P-SEP was determined to be 695 ng/L.Conclusion: P-SEP, when combined with IL-6 and CRP, may be utilized as a negative predictive marker of EOS (NPV 97.2%, 95% CI: 93.3–101), especially in newborns at low to medium risk of infection.

Mortality and morbidity of newborns with sepsis can be improved by early and accurate diagnosis and targeted therapy. To evaluate the early molecular events associated with inflammation and infection, we evaluated markers of endothelial activation and injury and circulating plasma miRNAs in preterm newborns with sepsis. The study group consisted of newborns with gestational age ≤ 32 weeks, with culture-positive early-onset neonatal sepsis (sepsis group, N = 8), and as a control group, we enrolled newborns without sepsis (control group, N = 12). Soluble markers of inflammation were measured using Luminex-based multiplex assay. Platelet-free plasma RNA was used to construct the library for miRNA sequencing analysis. Normalized counts were calculated and used to measure differential expression of individual detected miRNAs. We found a significant increase of interleukin 18 (IL-18) in the cord blood of the sepsis group (mean ± SEM, 104.7 ± 30.4 pg/ml vs 52.7 ± 5.6 pg/ml, P = 0.02). In peripheral blood of sepsis group patients, we found a significant increase of VEGF-A compared to controls (196.0 ± 70.5 pg/ml vs 59.6 ± 8.5 pg/ml, P = 0.02). In the cord blood plasma, eight miRNAs had significantly differential expression (P < 0.05), four miRNAs were up-regulated and four miRNAs down-regulated. In peripheral blood plasma, all nine miRNAs with significant differential expression were up-regulated. In conclusion, in early-onset neonatal sepsis, IL-18 and VEGF-A might be considered in diagnostic workup. Early-onset sepsis in preterm newborns is associated with significant changes in the circulating miRNA pattern.

Delayed umbilical cord clamping is a standard procedure for active management of the 3rd stage of labour. There are benefits associated with more than a 30 second delay, but 1 minute is usually recommended. For newborns, increased iron reserves are important having a positive impact on further development. A reduction in the risk of necrotizing enterocolitis and intraventricular hemorrhage is often reported in preterm births. In delayed umbilical cord clamping, no increased maternal blood loss was recorded, even in multiple pregnancies and caesarean sections.

The aim of this study was to assess the applicability of the neonatal sequential organ failure assessment score (nSOFA) within 72 h after delivery as a predictor for mortality and adverse outcome in very preterm neonates. Inborn neonates 2 was associated with OR 2.5 (CI 1.39–4.64, p = 0.002) for the adverse outcome. Area under the curve of ROC was 0.795 (95% CI = 0.763–0.827). The use of nSOFA seems to be reasonable for predicting mortality and morbidity in very preterm infants. It constitutes a suitable basis to measure the severity of organ dysfunction regardless of the cause.

Objective: There are minimal data available on nutrition after early repair of cleft lip and the factors influencing initiation of breastfeeding. This study assessed the impact of the length of surgery, length of ventilation support, and duration of hospital stay on breastfeeding rates after early cleft lip surgery. Design: This is a prospective observational cohort study comparing 2 hospitals providing early surgical repair of facial clefts from January 2014 to December 2016. Both hospitals are designated as Baby-Friendly Hospitals. Demographic and anthropometric data from mothers and newborns were recorded. Setting: Tertiary neonatal and pediatric surgery center. Patients: Hospital A: 61 newborns, Hospital B: 157 newborns. Interventions: Early (day 5 to 14) cheiloplasty in newborns with cleft lip or cleft lip and palate. Main Outcome Measures: Influence of duration of hospital stay, length of operation, and artificial ventilation on the rate of breastfeeding. Results: Significantly, more newborns were breastfed following early surgical repair of an isolated cleft lip compared to those with both cleft lip and palate, in both hospitals (hospital A 82% vs 0%, P = .0001, hospital B 66% vs 5%, P = .0001). Duration of hospital stay, length of operation, and duration of artificial ventilation did not significantly affect the rate of breastfeeding. Conclusions: The factors associated with early cleft lip repair (length of operation, length of ventilation support, and duration of hospital stay) do not affect breastfeeding rate.