Plasma Of Infants Research Articles

Fatty acids from nutrition sources for preterm infants and their effect on plasma fatty acid profiles

BackgroundIn preterm infants, IV administration of fat is less well tolerated compared to intake via the enteral route, often resulting in hypertriglyceridemia. It is therefore recommended that parenteral fat intake should not exceed 3.5 to 4.0 g/kg/d whereas human milk can provide up to 8 g/kg/d. It is unknown whether such hypertriglyceridemic conditions are caused by a uniform increase of all fatty acids or it is linked to an elevation of distinct fatty acids due to an unbalanced intake. Obviously, both scenarios could potentially influence the formulation of novel lipid solutions for preterm infants. Objective of this exploratory study was to compare fatty acid profiles between a) different nutritional sources and corresponding plasma samples, b) plasma of infants fed breast milk versus those receiving lipid emulsion, and c) plasma of infants with normal versus elevated triglyceride levels.MethodsForty-seven preterm infants < 36 weeks of gestation were included; fatty acid profiles were measured in serum samples and corresponding nutritional sources (breast milk and lipid emulsion) using gas chromatography/mass spectrometry.ResultsCompared to breast milk levels, plasma contained significantly lower C8:0, C10:0, C12:0, C14:0, C19:1n9, C18:3n3 (p < 0.0001). In contrast, relative abundance of C16:0, C18:0 and C20:4n6 was higher in plasma than in corresponding breast milk samples (p < 0.001) and lipid emulsion (p < 0.01). Compared to the corresponding lipid emulsion, the abundance of C18:2n6 and C18:3n3 was significantly lower in plasma (p < 0.001). Fatty acid profiles in plasma of infants fed breast milk compared to lipid emulsion were not markedly different. Hypertriglyceridemic samples showed elevated levels for C18:1n9 and C16:0 when compared with normotriglyceridemic samples.ConclusionsOur study reveals that lipid levels in plasma show both depletion and enrichment of distinct fatty acids which do not seem to be closely related to dietary intake. A more detailed understanding of fatty acid flux rates is needed, like the understanding of amino acid metabolism and is supported by the finding that hypertriglyceridemia might be a state of selective fatty acid accumulation. This would allow to develop more balanced diets for intensive care and potentially improve clinical outcomes.

Prolonged premature rupture of membranes with increased risk of infection is associated with gut accumulation of Pseudomonas from the environment

BackgroundPreterm premature rupture of membranes (PPROM) contributes to over one-third of preterm births, and PPROM infants are more susceptible to infections. However, the risk factors remain poorly understood. We here aim to investigate the association of duration of premature rupture of membranes (PROM) and environmental microbiota with the gut microbiota and infection in PPROM infants. MethodsForty-six premature infants were recruited from two hospitals, and infant fecal and environmental samples were collected. 16 s rRNA sequencing was performed to analyze the fecal and environmental microbiome. Human inflammatory cytokines in cord vein plasma were measured. ResultsThe gut microbiota composition of PPROM infants was different from that of non-PPROM infants, and the microbiome phenotypes were predicted to be associated with a higher risk of infection, further evidenced by the significantly increased levels of IL-6 and IL-8 in cord vein plasma of PPROM infants. The diversity of the gut microbiota in PPROM infants increased significantly as the duration of PROM excessed 12 h, and Pseudomonas contributed significantly to the dynamic changes. The Pseudomonas species in the gut of PPROM infants were highly homologous to those detected in the ward environment, suggesting that prolonged PROM is associated with horizontal transmission of environmental pathogens, leading to a higher risk of infection. ConclusionsThis study highlights that the duration of PROM is associated with the accumulation of environmental pathogens in the gut of PPROM infants, which is a risk factor for nosocomial infections. Improving environmental hygiene could be effective in optimizing the clinical care of PPROM infants.

Extracellular Vesicle ASC: A Novel Mediator for Lung-Brain Axis in Preterm Brain Injury.

Bronchopulmonary dysplasia (BPD) and neurodevelopmental impairment are among the most common morbidities affecting preterm infants. Although BPD is a predictor of poor neurodevelopmental outcomes, it is currently uncertain how BPD contributes to brain injury in preterm infants. Extracellular vesicles (EVs) are involved in interorgan communication in diverse pathological processes. ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain) is pivotal in inflammasome assembly and activation of inflammatory response. We assessed expression profiles of the alveolar macrophage (AM) markers CD11b, CD11c, and CD206 as well as ASC in EVs isolated from the plasma of preterm infants at risk for BPD at 1 week of age. We found that infants on higher fraction of inspired oxygen therapy (HO2⩾30%) had increased concentrations of AM-derived EV-ASC compared with infants on lower fraction of inspired oxygen (LO2<30%). To assess the function of these EVs, we performed adoptive transfer experiments by injecting them into the circulation of newborn mice. We discovered that mice that received EVs from infants on HO2 had increased lung inflammation, decreased alveolarization, and disrupted vascular development, the hallmarks of BPD. Importantly, these EVs crossed the blood-brain barrier, and the EVs from infants on HO2 caused inflammation, reduced cell survival, and increased cell death, with features of pyroptosis and necroptosis in the hippocampus. These results highlight a novel role for AM-derived EV-ASC in mediating the lung-to-brain cross-talk that is critical in the pathogenesis of BPD and brain injury and identify potential novel targets for preventing and treating BPD and brain injury in preterm infants.

Aryl hydrocarbon receptor (AhR) is regulated by hyperoxia in premature infants

Objective To investigate whether aryl hydrocarbon receptor (AhR) is involved in hyperoxia-mediated oxidative stress by observing the relationship between AhR and reactive oxygen species (ROS) in peripheral blood mononuclear cells (PBMCs) after oxygen exposure in premature infants. Methods After 48 h of oxygen inhalation at different concentrations, discarded peripheral blood was collected to separate PBMCs and plasma. ROS were labeled with MitoSOXTM Red and detected by fluorescence microscopy in PBMCs. The level of MDA in plasma was detected by thiobarbituric acid colorimetry, the level of MCP-1 in plasma was detected by enzyme-linked immunosorbent assay (ELISA), the localization of AhR was detected by immunofluorescence, and the level of AhR expression in PBMCs was detected by Western blotting. Results As the volume fraction of inspired oxygen increased, compared with those in the air control group, the levels of ROS, MDA in plasma, and MCP-1 in plasma increased gradually in the low concentration oxygen group, medium concentration oxygen group and high concentration oxygen group. The cytoplasm-nuclear translocation rate of AhR gradually increased, and the expression level of AhR gradually decreased. The levels of ROS in PBMCs, MDA in the plasma and MCP-1 in the plasma of premature infants were positively correlated with the cytoplasm-nuclear translocation rate of AhR but negatively correlated with the level of AhR expression. Conclusion Aryl hydrocarbon receptor (AhR) is regulated by hyperoxia in premature infants.

Обмін амінокислот як невід’ємна складова зростання передчасно народжених дітей (огляд літератури)

An important factor influencing the occurrence of metabolic disorders is premature birth. Compared to full-term children, prematurely born children are a special group of children in whom the morphology of organs and their physiological functions are not yet fully formed, and the activity of enzymes associated with protein metabolism is insufficient, which leads to disorders, including blocking the metabolism of certain amino acids. Thesis has been formed that certain factors will influence screening indicators of metabolic status in prematurely born children. The transition from the intrauterine environment, leading to a change from a state of complete dependence on the mother to an independent extrauterine environment, is perhaps the most dramatic physiological and metabolic event in life. Birth and early adaptation provoke the formation of significant changes in protein and energy metabolism. Amino acid concentrations are biomarkers of protein metabolism, and studying their patterns and levels in preterm infants may reveal metabolic changes associated with contributing factors. To date, standard values for the concentration of amino acids in the plasma of adults, infants and older children have been established. Since amino acids are important components of a large number of vital compounds, disruption of the physiological metabolism of the protein component can lead to growth retardation in a child born prematurely. Thesis has been formed that certain factors can influence screening indicators of metabolic status in prematurely born children. The purpose of the study was to summarize the literature data, understand the characteristics of the metabolism of individual amino acids in prematurely born children, and also systematize data on changes in amino acid levels against the background of perinatal pathology. Understanding and interpreting metabolic status provides a scientific basis and at the same time provides real-world guidance for improving the metabolic quality of care for preterm infants. No conflict of interests was declared by the authors.

Perinatal asphyxia does not influence presepsin levels in neonates: A prospective study.

To compare Presepsin (presepsin) levels in plasma and urine of uninfected newborn infants with perinatal asphyxia with those of controls. In this prospective study, we enrolled 25 uninfected full-term infants with perinatal asphyxia and 19 controls. We measured presepsin levels in whole blood or urine. In neonates with perinatal asphyxia, we compared presepsin levels in blood and urine at four time points. In neonates with perinatal asphyxia, blood and urinary presepsin levels matched each other at any time point. At admission, the median presepsin value in blood was similar in both groups (p = 0.74), while urinary levels were higher in hypoxic neonates (p = 0.05). Perinatal asphyxia seemed to increase serum CRP and procalcitonin levels beyond normal cut-off but not those of presepsin. In uninfected neonates with perinatal asphyxia, median blood and urinary presepsin levels matched each other at any point in the first 72 h of life and seemed to be slightly affected by the transient renal impairment associated with perinatal hypoxia in the first 12 h of life. Perinatal asphyxia did not influence presepsin levels within the first 72 h of life, while those of CRP and procalcitonin increased.

Physiologically-based pharmacokinetic model to predict doxorubicin and paclitaxel exposure in infants through breast milk.

Limited information is available concerning infant exposure and safety when breastfed by mothers receiving chemotherapy. Whereas defining distribution to breast milk is important to infer drug exposure, infant pharmacokinetics also determine to what extent the infant will be exposed to potential toxic effects. We aimed to assess the impact of chemotherapy containing breast milk on infants by predicting systemic and local (intestinal) exposure of paclitaxel and doxorubicin in infants through breast milk using a physiologically-based pharmacokinetic (PBPK) approach. Whole-body PBPK models of i.v. paclitaxel and doxorubicin were extended from the literature, with an oral absorption component to enable predictions in infants receiving paclitaxel or doxorubicin-containing breast milk. For safety considerations, worst-case scenarios were explored. Finally, paclitaxel and doxorubicin exposures in plasma and intestinal tissue of infants following feeding of breast milk from paclitaxel- or doxorubicin-treated mothers were simulated and breast milk discarding strategies were evaluated. The upper 95th percentile of the predicted peak concentrations in peripheral venous blood were 3.48 and 0.74 nM (0.4%-1.7% and 0.1%-1.8% of on-treatment) for paclitaxel and doxorubicin, respectively. Intestinal exposure reached peak concentrations of 1.0 and 140 μM for paclitaxel and doxorubicin, respectively. Discarding breast milk for the first 3 days after maternal chemotherapy administration reduced systemic and tissue exposures even further, to over 90% and 80% for paclitaxel and doxorubicin, respectively. PBPK simulations of chemotherapy exposure in infants after breastfeeding with chemotherapy containing breast milk suggest that particularly local gastrointestinal adverse events should be monitored, whereas systemic adverse events are not expected.

Contribution of ADD3 and the HLA Genes to Biliary Atresia Risk in Chinese.

Nonsyndromic biliary atresia (BA) is a rare polygenic disease, with autoimmunity, virus infection and inflammation thought to play roles in its pathogenesis. We conducted a genome-wide association study in 336 nonsyndromic BA infants and 8900 controls. Our results validated the association of rs17095355 in ADD3 with BA risk (odds ratio (OR) = 1.70, 95% confidence interval (95% CI) = 1.49-1.99; p = 4.07 × 10-11). An eQTL analysis revealed that the risk allele of rs17095355 was associated with increased expression of ADD3. Single-cell RNA-sequencing data and immunofluorescence analysis revealed that ADD3 was moderately expressed in cholangiocytes and weakly expressed in hepatocytes. Immuno-fluorescent staining showed abnormal deposition of ADD3 in the cytoplasm of BA hepatocytes. No ADD3 auto-antibody was observed in the plasma of BA infants. In the HLA gene region, no variants achieved genome-wide significance. HLA-DQB1 residue Ala57 is the most significant residue in the MHC region (OR = 1.44, 95% CI = 1.20-1.74; p = 1.23 × 10-4), and HLA-DQB1 was aberrantly expressed in the bile duct cells. GWAS stratified by cytomegalovirus (CMV) IgM status in 87 CMV IgM (+) BA cases versus 141 CMV IgM (-) BA cases did not yield genome-wide significant associations. These findings support the notion that common variants of ADD3 account for BA risk. The HLA genes might have a minimal role in the genetic predisposition of BA due to the weak association signal. CMV IgM (+) BA patients might not have different genetic risk factor profiles compared to CMV IgM (-) subtype.

A Study of the Literature on Intrauterine Treatment Options for Chronic Placental Insufficiency with Intrauterine Growth Restriction Using Intrauterine Intravascular Amino Acid Supplementation.

Intrauterine growth retardation (IUGR) is a very serious prenatal condition with 3-5% incidence of all pregnancies. It results from numerous factors, including chronic placental insufficiency. IUGR is associated with an increased risk of mortality and morbidity and is considered a major cause of fetal mortality. Currently, treatment options are significantly limited and often result in preterm delivery. Postpartum, IUGR infants also have higher risks of disease and neurological abnormalities. The PubMed database was searched using the keywords "IUGR", "fetal growth restriction", "treatment", "management" and "placental insufficiency" for the period between 1975 and 2023. These terms were also combined together. There were 4160 papers, reviews and articles dealing with the topic of IUGR. In total, only 15 papers directly dealt with a prepartum therapy of IUGR; 10 of these were based on an animal model. Overall, the main focus was on maternal intravenous therapy with amino acids or intraamniotic infusion. Treatment methods have been tested since the 1970s to supplement the fetuses with nutrients lacking due to chronic placental insufficiency in various ways. In some studies, pregnant women were implanted with a subcutaneous intravascular perinatal port system, thus infusing the fetuses with a continuous amino acid solution. Prolongation of pregnancy was achieved, as well as improvement in fetal growth. However, insufficient benefit was observed in infusion with commercial amino acid solution in fetuses below 28 weeks' gestation. The authors attribute this primarily to the enormous variation in amino acid concentrations of the commercially available solutions compared with those observed in the plasma of preterm infants. These different concentrations are particularly important because differences in the fetal brain caused by metabolic changes have been demonstrated in the rabbit model. Several brain metabolites and amino acids were significantly decreased in IUGR brain tissue samples, resulting in abnormal neurodevelopment with decreased brain volume. There are currently only a few studies and case reports with correspondingly low case numbers. Most of the studies refer to prenatal treatment by supplementation of amino acids and nutrients to prolong pregnancy and support fetal growth. However, there is no infusion solution that matches the amino acid concentrations found in fetal plasma. The commercially available solutions have mismatched amino acid concentrations and have not shown sufficient benefit in fetuses below 28 weeks' gestation. More treatment avenues need to be explored and existing ones improved to better treat multifactorial IUGR fetuses.

Safety, efficacy, and pharmacokinetics of delgocitinib ointment in infants with atopic dermatitis: A phase 3, open-label, and long-term study

BackgroundDelgocitinib ointment, a topical Janus kinase inhibitor, is used as treatment of patients with atopic dermatitis (AD) aged ≥2 years in Japan. Although initiating appropriate and early treatment upon the onset of AD in childhood is important, the safety and efficacy of delgocitinib ointment in infants with AD have not been established. MethodsThis phase 3 study was conducted from October 2020 to June 2022 (number JapicCTI-205412). Eligible Japanese infants with AD aged 6 to <24 months received 0.25% or 0.5% of delgocitinib ointment twice daily for 52 weeks in an open-label uncontrolled manner. Topical corticosteroids were allowed to apply for worsening AD during the treatment period at the investigators’ discretion. ResultsA total of 22 infants were enrolled. Adverse events (AEs) were reported in 21 (95.5%) infants and were mostly mild. No treatment-related AEs were reported. The Modified Eczema Area and Severity Index (mEASI) score continuously decreased until week 4, and the score reduction was maintained until week 52. The mean percent changes in the mEASI score from baseline were −73.5% at week 4, −81.7% at week 28, and −81.9% at week 52. Delgocitinib was not detected in the plasma of most infants (68.2%–95.2%). ConclusionsDelgocitinib ointment is well tolerated and effective for up to 52 weeks when applied to Japanese infants with AD.

Determination of caffeine, paraxanthine, theophylline and theobromine in premature infants by HILIC-MS/MS

Aim: Caffeine is a central nervous system stimulant, used to treat apnea of prematurity. A hydrophilic interaction chromatography-tandem mass spectrometry(HILIC-MS/MS) approach was developed to detect caffeine, paraxanthine, theophyllineand theobromine in premature infants. Method: Protein precipitation of plasma samples (10μl) was carried out by treating with acetonitrile containing caffeine-13C3. The separation was carried out on an ACQUITY HPLC® BEH HILIC column. Caffeine and its metabolites were quantified by multiple reaction monitoring modes with positive electrospray ionization. Results: The established method had a good linear relationship in the range of 0.0600-60.0μg/ml for caffeine, 0.0250-7.50μg/ml for theobromine and0.0150-4.50μg/ml for paraxanthine and theophylline. Conclusion: A HILIC-MS/MS method was developed and validated to determine caffeine and its major metabolites in plasma of premature infants.

Use of Fresh-frozen Plasma in Newborn Infants.

Nearly 10% of premature and critically ill infants receive fresh-frozen plasma (FFP) transfusions to reduce their high risk of bleeding. The authors have only limited data to identify relevant clinical predictors of bleeding and to evaluate the efficacy of FFP administration. There is still no consensus on the optimal use of FFP in infants who have abnormal coagulation parameters but are not having active bleeding. The aims of this review are to present current evidence derived from clinical studies focused on the use of FFP in neonatology and then use these data to propose best practice recommendations for the safety of neonates receiving FFP.

Next-generation biomonitoring of the early-life chemical exposome in neonatal and infant development

Exposure to synthetic and natural chemicals is a major environmental risk factor in the etiology of many chronic diseases. Investigating complex co-exposures is necessary for a holistic assessment in exposome-wide association studies. In this work, a sensitive liquid chromatography-tandem mass spectrometry approach was developed and validated. The assay enables the analysis of more than 80 highly-diverse xenobiotics in urine, serum/plasma, and breast milk; with detection limits generally in the pg-ng mL−1 range. In plasma of extremely-premature infants, 27 xenobiotics are identified; including contamination with plasticizers, perfluorinated alkylated substances and parabens. In breast milk samples collected longitudinally over the first 211 days post-partum, 29 analytes are detected, including pyrrolizidine- and tropane alkaloids which have not been identified in this matrix before. A preliminary estimation of daily toxicant intake via breast milk is conducted. In conclusion, we observe significant early-life co-exposure to multiple toxicants, and demonstrate the method’s applicability for large-scale exposomics-type cohort studies.

Prenatal opioid-exposed infant extracellular miRNA signature obtained at birth predicts severity of neonatal opioid withdrawal syndrome

Prenatal opioid exposure (POE) is commonly associated with neonatal opioid withdrawal syndrome (NOWS), which is characterized by a broad variability in symptoms and severity. Currently there are no diagnostic tools to reliably predict which infants will develop severe NOWS, while risk stratification would allow for proactive decisions about appropriate clinical monitoring and interventions. The aim of this prospective cohort study was to assess if extracellular microRNAs (miRNAs) in umbilical cord plasma of infants with POE could predict NOWS severity. Participants (n = 58) consisted of pregnant women receiving medications for opioid use disorder and their infants. NOWS severity was operationalized as the need for pharmacologic treatment and prolonged hospitalization (≥ 14 days). Cord blood miRNAs were assessed using semi-quantitative qRT-PCR arrays. Receiver operating characteristic curves and area under the curve (AUC) were estimated. The expression of three miRNAs (miR-128-3p, miR-30c-5p, miR-421) predicted need for pharmacologic treatment (AUC: 0.85) and prolonged hospitalization (AUC: 0.90). Predictive validity improved after two miRNAs (let-7d-5p, miR-584-5p) were added to the need for pharmacologic treatment model (AUC: 0.94) and another two miRNAs (let-7b-5p, miR-10-5p) to the prolonged hospitalization model (AUC: 0.99). Infant cord blood extracellular miRNAs can proactively identify opioid-exposed neonates at high-risk for developing severe NOWS.

Hsa_circ_0009057 can be a novel potential diagnostic biomarker and a therapeutic target for premature brain injury

Circular RNAs (CircRNAs) represent a novel class of noncoding RNAs, and are widely expressed in brain tissues, indicating their great potential as novel biomarkers for the diagnosis of neuropsychiatric disorders. However, the expression profiles of circRNAs for infants with premature brain injury (PBI) have not been fully explored. This study assessed the differentially expressed circRNAs in plasma of infants with and without PBI using the human circRNA microarray analysis. Hsa_circ_0009057, a significantly up-regulated circRNA in infants with PBI, was selected for further study. The microRNA (miRNA)-recognition element prediction analysis and construction of the circRNA-miRNA-mRNA network showed that hsa_circ_0009057 was associated with several miRNAs and mRNAs, which played important roles in the regulation of neuropsychiatric disorders. The results of the receiver operating characteristic curve analysis showed that hsa_circ_0009057 had high degrees of specificity and sensitivity. The results also indicated that hsa_circ_0009057 could be served as a novel potential diagnostic biomarker and a therapeutic target for PBI.

Increased Levels of Plasma Extracellular Heat-Shock Proteins 60 and 70 kDa Characterized Early-Onset Neonatal Sepsis.

Background: Extracellular heat-shock proteins (eHsp) are highly conserved molecules that play an important role in inflammatory diseases and have been quantified in plasma from patients with infectious diseases, including sepsis. There is a constant search for dependable biochemical markers that, in combination with conventional methods, could deliver a prompt and reliable diagnosis of early-onset neonatal sepsis.Objective: We sought to assess the level of eHsp-27, eHsp-60, eHsp-70, and tumor necrosis factor-alpha (TNFα) in plasma of healthy neonates at term and infants with early-onset neonatal sepsis.Methods: This study included 34 newborns that were classified as healthy neonates at term (blood samples from the umbilical cord, n = 23) or infants with early-onset neonatal sepsis (blood samples obtained from umbilical artery by standard sterile procedures before starting a systemic antibiotic intervention, n = 11). All blood samples were centrifuged, and the plasma recovered to determine eHsp-27, eHsp-60, eHsp-70, and TNFα levels by ELISA.Results: Our results indicate that the level of eHsp-27 in healthy neonates at term was 0.045 ± 0.024 pg/ml. This value decreased 2.5-fold in infants with early-onset neonate sepsis (0.019 ± 0.006 pg/ml, p = 0.004). In contrast, the levels of eHsp-60 and eHsp-70 in healthy neonates at term were 13.69 ± 5.3 and 4.03 ± 2.6 pg/ml, respectively. These protein levels increased significantly 1.8- and 1.9-fold in the plasma of infants with early-onset neonatal sepsis (p ≤ 0.001). The level of TNFα in healthy neonates at term was 2.94 ± 0.46 pg/ml, with a 3.0-fold increase in infants with early-onset neonatal sepsis (8.96 ± 0.72 pm/ml, p ≤ 0.001). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of eHsp compared with that of C-reactive protein were 73.3, 60.0, 47.8, and 33.3%, respectively.Conclusion: This study demonstrated a consistent increase of eHsp-60 and eHsp-70 in the plasma of infants diagnosed with early-onset neonatal sepsis. These proteins showed higher sensitivity and specificity than C-reactive protein and blood culture test.

The Effect of Platelets on Thrombin Generation in Cord Blood and Peripheral Neonatal Blood in the Premature Infant; The Event Study

IntroductionInfants born very preterm (<32 weeks) are at increased risk of haemorrhage, particularly intraventricular haemorrhage which can result in short and long term morbidity. Routine clinical laboratory tests such as the prothrombin time and activated partial thromboplastin time are frequently abnormal in this patient group but do not appear to correlate with clinical outcomes. Moreover, while reduced levels of circulating coagulation factors and platelet hypo-reactivity have been reported, plasma thrombin generation (TG), has been reported to be similar or even enhanced in very preterm infants when compared to term infants.Extracellular vesicles, comprising of lipid-bound nanoparticles released from cells (including platelets), may potentially play a role in modulating neonatal haemostasis. We aimed to characterize phospholipid (PL)-dependent plasma thrombin generation in platelet-rich (PRP) and platelet-poor plasma (PPP) in premature infants in both umbilical cord blood & peripheral neonatal blood using calibrated automated thrombography (CAT).MethodsIn this prospective observational study, PRP and PPP was prepared by centrifugation from citrated umbilical cord blood and peripheral neonatal blood collected from premature infants (24 - 31 weeks) and healthy term controls (>37 weeks). No samples were collected from heparinised lines. Parameters of plasma thrombin generation in PRP were assessed using CAT, with thrombin generation stimulated by tissue factor only (TF; final concentration 1pM). CAT was also repeated in PPP using only TF and no exogenous PL (rendering the assay dependent upon the endogenous PL content of plasma).ResultsIn the analysis of umbilical cord blood PRP, plasma thrombin generation was accelerated in the preterm infant group with a significantly shorter time to peak TG observed. The other parameters of TG were similar in both groups (Table 1).In the subset of infants from whom peripheral blood samples were available, there was further evidence of enhanced plasma TG in preterm PRP relative to term infants (Table 2). In this subgroup, the lag time and time to peak thrombin were significantly shorter in the preterm group and peak thrombin was significantly higher.TG was also assessed in both PPP and PRP prepared from umbilical cord blood samples in a subgroup of infants (n=10 term, n=6 preterm) using 1pM TF only, rendering the assay dependent on the phospholipid content of plasma. No difference was observed in any CAT parameters, suggesting that neonatal PPP phospholipid content (potentially from circulating extracellular vesicles) is sufficient to support thrombin generation in the absence of exogenous phospholipid.ConclusionThese preliminary data suggest that neonatal PRP, measured in both umbilical cord blood and peripheral neonatal blood, has similar thrombin generation or may even be hypercoagulable, compared with healthy term controls. Moreover, neonatal plasma phospholipid appears to support thrombin generation in the absence of exogenous phospholipid. This ongoing prospective study aims to further characterize the platelet-dependency of neonatal thrombin generation and evaluate the potential role of extracellular vesicles in neonatal haemostasis. [Display omitted] DisclosuresMaguire: Actelion: Research Funding; Bayer Pharma: Research Funding. Ni Ainle: Leo Pharma: Research Funding; Actelion: Research Funding; Daiichi-Sankyo: Research Funding; Bayer Pharma: Research Funding.

THE LEVEL OF INDICES OF ION COMPOSITION OF BLOOD IN INFANTS WITH CONGENITAL MALFORMATIONS IN SURGICAL CORRECTION

Newborns with severe congenital malformations need radical surgical correction as soon as possible for ensure the quality of life of the infant in the future. Pathological changes associated with the underlying pathology may be accompanied to severe disturbances of homeostasis in the postoperative period.&#x0D; The aim of the study. To assess the level of ionic composition of plasma in infants with congenital malformations during surgical correction and various types of combined anesthesia.&#x0D; Investigated problem: To prevent electrolyte peri- and postoperative complications, it is obligatory to perform preoperative preparation and stabilization of laboratory parameters, for a child with congenital malformations and to monitor they throughout the operation.&#x0D; The main scientific results: The electrolyte composition in the examined groups of infants did not show significant differences from age norms. The concentration of potassium was the lowest in group III of the examined in comparison with groups I and II at the stage of preparation for surgery (p=0.0041; p=0.0102), induction of anesthesia (p=0.0053; p=0.0054), while children of groups I and II were diagnosed with a tendency to the upper limit of normal serum potassium levels during all observation periods. Elevated sodium levels were diagnosed in group III at all stages of surgical treatment and in group II of infants with congenital malformations at the stage of the most painful and traumatic moment of surgery (159.94±4.89 – II, 139.27±3.043 – III, p=0.1857).&#x0D; The area of practical use of the research results: pediatric anesthesiology&#x0D; Innovative technological product: laboratory control&#x0D; Scope of the innovative technological product: neonatal intensive care unit, surgery

Glucose profiles in healthy term infants in the first 5 days: the glucose in well babies (GLOW) study

Objectives To determine postnatal changes in plasma and interstitial glucose concentrations of healthy infants receiving current recommended care and to compare the incidence of low concentrations with recommended thresholds for treatment of at-risk infants. Study design A prospective masked observational study in Hamilton, New Zealand. Healthy, term, appropriately grown singletons had continuous glucose monitoring and repeated heel-prick plasma glucose measurements (4 in the first 24 hours then twice daily using the glucose oxidase method) from birth to 120 hours. Results The 67 infants had a mean birth weight of 3584 ± 349 g, and gestational age of 40.1 ± 1.2 weeks. The mean glucose concentrations increased over the first 18 hours, remained stable to 48 hours (59 ± 11 mg/dL; 3.3 ± 0.6 mmol/L)] before increasing to a new plateau by the fourth day (89 ± 13 mg/dL; 4.6 ± 0.7 mmol/L). Plasma glucose concentrations of 47 mg/dL (2.6 mmol/L) approximated the 10th percentile in the first 48 hours, and 39% of infants had ≥1 episode below this threshold. Early term infants had lower mean glucose concentrations than those born at later gestational ages and were more likely to have episodes Conclusions Healthy infants seem to complete their metabolic transition by day 4. Many have glucose concentrations below the accepted thresholds for treatment of hypoglycemia. Trial registration ACTRN: 12615000986572.

MicroRNA analysis of childhood atopic dermatitis reveals a role for miR-451a.

MicroRNAs (miRNAs), important regulators of gene expression, have been implicated in a variety of disorders. The expression pattern of miRNAs in paediatric atopic dermatitis (AD) has not been well studied. We sought to investigate miRNA expression profiles in different blood compartments of infants with AD. Small RNA and analysis with the HTG EdgeSeq system were performed to identify differentially expressed miRNAs in peripheral blood mononuclear cells (PBMCs) and plasma of infants with AD vs. age-matched healthy controls, with reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) used for validation and measurement of miRNA targets. Logistic regression models with area under the receiving operating characteristic estimation was used to evaluate the diagnostic potential of chosen miRNAs for AD. RNA sequencing was performed to access miRNA expression profiles in paediatric AD. We identified 10 differentially expressed miRNAs in PBMCs and eight dysregulated miRNAs in plasma of infants with AD compared with controls. Upregulated miRNAs in PBMCs included miRNAs known to be involved in inflammation: miR-223-3p, miR-126-5p and miR-143-3p. Differential expression of only one miRNA, miR-451a, was observed in both PBMCs and plasma of children with AD. Dysregulation of three miRNAs (miR-451a, miR-143-3p and miR-223-3p) was validated in larger numbers of samples and miR-451a was identified as a predictive biomarker for the early diagnosis of the disease. Experimentally verified targets of miR-451a, interleukin 6 receptor (IL6R) and proteasome subunit beta type-8 (PSMB8), were increased in patients with AD, negatively correlated with miR-451a levels and upregulated following inhibition of miR-451a in PBMCs. In infants with AD, a distinct peripheral blood miRNA signature is seen, highlighting the systemic effects of the disease. miR-451a is uniquely expressed in different blood compartments of patients with AD and may serve as a promising novel biomarker for the early diagnosis of AD.