Antimicrobial Peptides in Early-Life Host Defense, Perinatal Infections, and Necrotizing Enterocolitis-An Update.

Host defense against early-life infections such as chorioamnionitis, neonatal sepsis, or necrotizing enterocolitis (NEC) relies primarily on innate immunity, in which antimicrobial peptides (AMPs) play a major role. AMPs that are important for the fetus and neonate include α and ß defensins, cathelicidin LL-37, antiproteases (elafin, SLPI), and hepcidin. They can be produced by the fetus or neonate, the placenta, chorioamniotic membranes, recruited neutrophils, and milk-protein ingestion or proteolysis. They possess antimicrobial, immunomodulating, inflammation-regulating, and tissue-repairing properties. AMPs are expressed as early as the 13th week and increase progressively through gestation. Limited studies are available on AMP expression and levels in the fetus and neonate. Nevertheless, existing evidence supports the role of AMPs in pathogenesis of chorioamnionitis, neonatal sepsis, and NEC, and their association with disease severity. This suggests a potential role of AMPs in diagnosis, prevention, prognosis, and treatment of sepsis and NEC. Herein, we present an overview of the antimicrobial and immunomodulating properties of human AMPs, their sources in the intrauterine environment, fetus, and neonate, and their changes during pre- and post-natal infections and NEC. We also discuss emerging data regarding the potential utility of AMPs in early-life infections, as diagnostic or predictive biomarkers and as therapeutic alternatives or adjuncts to antibiotic therapy considering the increase of antibiotic resistance in neonatal intensive care units.

Management of antibiotic allergy in children: a practical approach.

BACKGROUND: About 10% of children are declared as allergic to antibiotics, with beta(ß)-lactams being the most common perpetrators. However, few of these are confirmed by allergy tests. This characteristic of being allergic follows a child well into adulthood, leading to alternative, usually more expensive broad-spectrum antibiotics, contributing to antibiotic resistance and increasing healthcare expenses. OBJECTIVE: This review presents a practical approach to managing pediatric patients with antibiotic hypersensitivity reactions. MATERIAL AND METHODS: We updated the guidelines on antibiotic allergy in children by conducting systematic literature research using the best available evidence from PubMed search by entering the keywords "antibiotic allergy" and "children." The search output yielded 5165 citations. RESULTS: Management of antibiotic allergy depends on the culprit antibiotic, and it includes confirmation of the diagnosis and finding a safe alternative to the culprit antibiotic. In particular patients with a history indicative of penicillin allergy can be treated with cephalosporins as an alternative to penicillin, especially with third-generation cephalosporins, except for those with similar R1 side chains. In patients with a history of immediate-type reactions to cephalosporins who require treatment with cephalosporins or penicillin, skin tests with cephalosporin or penicillin with different side chains should be performed. If allergy to macrolides is suspected, challenge tests are currently the only reliable diagnostic tool. The best strategy for managing patients with sulfonamide hypersensitivity is an alternative antibiotic. The skin prick tests and intradermal tests are not recommended for diagnosis of quinolone allergy, as they can activate dermal mast cells leading to false-positive results. Quinolone challenge test is the most appropriate test for diagnosing quinolone hypersensitivity. CONCLUSION: Although adverse drug reactions to antibiotics are frequently documented, immunologically mediated hypersensitivity is unusual. In the event of an reaction, an appropriate diagnostic workup is required to identify the drug's causal role. It is critical to avoid "labeling" a child as allergic without first conducting a proper diagnostic workup.

Management of antibiotic allergy in children: a practical approach

Background: About 10% of children are declared as allergic to antibiotics, with beta(β)-lactams being the most common perpetrators. However, few of these are confirmed by allergy tests. This characteristic of being allergic follows a child well into adulthood, leading to alternative, usually more expensive broad-spectrum antibiotics, contributing to antibiotic resistance and increasing healthcare expenses.Objective: This review presents a practical approach to managing pediatric patients with antibiotic hypersensitivity reactions.Material and methods: We updated the guidelines on antibiotic allergy in children by conducting systematic literature research using the best available evidence from PubMed search by entering the keywords “antibiotic allergy” and “children.” The search output yielded 5165 citations.Results: Management of antibiotic allergy depends on the culprit antibiotic, and it includes confirmation of the diagnosis and finding a safe alternative to the culprit antibiotic. In particular patients with a history indicative of penicillin allergy can be treated with cephalosporins as an alternative to penicillin, especially with third-generation cephalosporins, except for those with similar R1 side chains. In patients with a history of immediate-type reactions to cephalosporins who require treatment with cephalosporins or penicillin, skin tests with cephalosporin or penicillin with different side chains should be performed. If allergy to macrolides is suspected, challenge tests are currently the only reliable diagnostic tool. The best strategy for managing patients with sulfonamide hypersensitivity is an alternative antibiotic. The skin prick tests and intradermal tests are not recommended for diagnosis of quinolone allergy, as they can activate dermal mast cells leading to false-positive results. Quinolone challenge test is the most appropriate test for diagnosing quinolone hypersensitivity (AU)

Diet Quality: A Neglected Parameter in Children With Food Allergies. A Cross-Sectional Study.

Background-Objective: With recent evidence suggesting that growth is no longer considered a major issue in children with food allergies (FA) on elimination diet, priority has shifted to diet quality to establish healthy eating patterns and prevent non-communicable diseases. The Diet Quality Index - International (DQI-I) could be useful for assessing the overall diet quality of FA-children. This study aimed to evaluate the impact of elimination diet on DQI-I in children with FA and the accuracy of DQI-I in reflecting nutrient intake. Materials-methods: In a prospective, cross-sectional, cohort study of FA-children (2-14 years), nutritional intake was evaluated using a 7-day food frequency questionnaire, 24-h dietary recall, and the DQI-I. Results: Of the 76 children recruited, 44.7% had multiple allergies. Mean overall DQI-I score was 52 points, with only 28% of participants having good overall DQI-I (≥60 points). DQI-I moderation and balance were the most affected domains. Participants with multiple allergies had higher DQI-I moderation and balance and lower vitamin D and Ca intake. Compared to toddlers, schoolchildren had higher DQI-I variety and lower moderation and received higher vitamin B2, vitamin B12, Ca, P, and Zn. The number of allergies, age, and milk avoidance were independently associated with adjusted DQI-I moderation and balance, energy, and certain micronutrient intake. Higher percentages of participants with good DQI-I received adequate amounts of Mn and vitamins A, B6, C, and folate than those with poor DQI-I. Conclusions: In children with FA on elimination diet, the DQI-I accurately captured the deflection of diet quality related to the development of chronic, non-communicable diseases through its moderation and balance components. This is DQI-I's main purpose as a healthy diet indicator and as such it would be a useful tool responding to the needs of the contemporary shifting of priorities in FA-children's diet from quantity to quality. Nevertheless, it does not accurately reflect the intake of certain micronutrients potentially compromised by elimination diets. Therefore, regular nutritional assessment utilizing both the DQI-I and tools assessing individual nutrient intakes along with professional nutrition counseling should be integral parts of the individualized management of children with FA to ensure adequate nutrient intake and establish healthy dietary patterns.

A Novel Mutation of VPS33B Gene Associated with Incomplete Arthrogryposis-Renal Dysfunction-Cholestasis Phenotype.

Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome is an autosomal recessive disorder caused by mutations of the VPS33B encoding the vacuolar protein sorting 33B (VPS33B), which is involved in the intracellular protein sorting and vesicular trafficking. We report a rare case of ARC syndrome without arthrogryposis caused by a novel mutation of VPS33B. A female patient of Greek origin presented on the 14th day of life with renal tubular acidosis, Fanconi syndrome, nephrogenic diabetes insipidus, and cholestasis with normal gamma-glutamyl transpeptidase, without arthrogryposis and dysmorphic features. She was born to apparently healthy, nonconsanguineous parents. Additional features included dry and scaling skin, generalized hypotonia, hypoplastic corpus callosum, neurodevelopmental delay, failure to thrive, short stature, recurrent febrile episodes with and without infections, and gastrointestinal bleeding. DNA testing revealed that the patient was homozygous for the novel c.1098_1099delTG (p.Glu367Alafs∗17) mutation of exon 14 of VPS33B gene (NM_018668) on chromosome 15q26.1, leading to a nonsense frameshift variant of VPS33B with premature termination of translation. Her parents were heterozygous for the same VPS33B mutation. The prognosis was predictably poor in the context of the intractable polyuria necessitating long-term parenteral fluid administration via indwelling central catheter leading to catheter-related sepsis, to which she eventually succumbed at the age of 7 months. This is the first published VPS33B mutation in an ARC patient of Greek origin. The current case adds to the spectrum of ARC-associated VPS33B mutations and provides evidence supporting the existence of incomplete ARC phenotype. Increased awareness and early genetic testing for ARC are suggested in cases with isolated cholestasis and/or renal tubular dysfunction, even in the absence of arthrogryposis.

Inflammatory Bowel Disease in Children and Adolescents - a Retrospective Study of 13 Years of Records Investigating Potential Prognostic Factors.

Purpose: To assess the landscape of management of pediatric inflammatory bowel disease (IBD) patients in Greece and investigate possible prognostic factors for the disease outcome. Method: The medical records of all IBD patients who visited the gastroenterology divisions of two university pediatric clinics as in- or outpatients over 13 years were examined. Results: Twenty-seven females and 25 males were included in the study. Ulcerative colitis (UC) was diagnosed in 46% of cases, Crohn's Disease (CD) in 33% and unclassified IBD (IBD-U) remained the diagnosis in 21%. The CRP level was elevated in 68% of cases at diagnosis, whereas only 27.4% of patients had ESR levels and platelet counts within the age-adjusted normal range. No parameter derived from patient history, physical examination or laboratory and imaging was found to influence the time to diagnosis. Abdominal pain and lack of diarrhea at the time of diagnosis were significantly associated with the need for biologic therapy during the disease course in CD. Consistent with the "step-up" approach the treating physicians practiced, an increased number of relapses correlated with the addition of biologics in the treatment of both CD and UC patients (P=.03 and P=.002, respectively). Conclusion: It is the first time that clinical data regarding IBD pediatric patients in Greece were reviewed. Some clinical and imaging factors were associated with more aggressive disease, an increased need for biological treatment and frequent hospitalizations for IBD flares. Moreover, it was observed that the clinical features of IBD in Greek children were similar to those in other countries.

Emerging Biomarkers for Prediction and Early Diagnosis of Necrotizing Enterocolitis in the Era of Metabolomics and Proteomics.

Necrotizing Enterocolitis (NEC) is a catastrophic disease affecting predominantly premature infants and is characterized by high mortality and serious long-term consequences. Traditionally, diagnosis of NEC is based on clinical and radiological findings, which, however, are non-specific for NEC, thus confusing differential diagnosis of other conditions such as neonatal sepsis and spontaneous intestinal perforation. In addition, by the time clinical and radiological findings become apparent, NEC has already progressed to an advanced stage. During the last three decades, a lot of research has focused on the discovery of biomarkers, which could accurately predict and make an early diagnosis of NEC. Biomarkers used thus far in clinical practice include acute phase proteins, inflammation mediators, and molecules involved in the immune response. However, none has been proven accurate enough to predict and make an early diagnosis of NEC or discriminate clinical from surgical NEC or other non-NEC gastrointestinal diseases. Complexity of mechanisms involved in NEC pathogenesis, which remains largely poorly elucidated, could partly explain the unsatisfactory diagnostic performance of the existing NEC biomarkers. More recently applied technics can provide important insight into the pathophysiological mechanisms underlying NEC but can also aid the detection of potentially predictive, early diagnostic, and prognostic biomarkers. Progress in omics technology has allowed for the simultaneous measurement of a large number of proteins, metabolic products, lipids, and genes, using serum/plasma, urine, feces, tissues, and other biological specimens. This review is an update of current data on emerging NEC biomarkers detected using proteomics and metabolomics, further discussing limitations and future perspectives in prediction and early diagnosis of NEC.

Early Postnatal Changes of Bone Turnover Biomarkers in Very Low-Birth-Weight Neonates-The Effect of Two Parenteral Lipid Emulsions with Different Polyunsaturated Fatty Acid Content: A Randomized Double-Blind Study.

BACKGROUND: ω-3 polyunsaturated fatty acids (n-3 PUFAs) are reported to have beneficial effect on bone mineral density. This study aimed to evaluate early changes of bone turnover biomarkers in very low-birth-weight (VLBW) neonates and the effect of 2 parenteral lipid emulsions (PLEs) with different PUFA composition. METHODS: This is a randomized double-blind study with parallel design. VLBW neonates (n = 66) receiving parenteral nutrition (PN)>70% of daily energy requirements for >14 days were assigned into 2 groups that were prescribed soybean oil-based (n = 35) and n-3-enriched PLE (n = 31), respectively. Osteoprotegerin (OPG), soluble receptor activator of nuclear factor-kB ligand (sRANKL), osteocalcin (OC), interleukin-6 (enzyme-linked immunoblot assay kits), Ca, and P plasma levels were assessed before PLE implementation (T1) and on day 20 of life (T2). RESULTS: In the total population, sRANKL and OC significantly increased, whereas OPG and the OPG/sRANKL ratio decreased from T1 to T2. Within each group, T1-to-T2 changes of OC were significant in both groups, whereas those of OPG/sRANKL were significant only in the soybean-based group. Multiple regressions showed an independent effect of group allocation on OPG change. Significant associations were observed between PN duration and sRANKL change (negatively), n-6/n-3 and OC changes (positively), and OPG and sRANKL changes (positively). CONCLUSIONS: A high bone-turnover rate in VLBW neonates with predominance of bone resorption is confirmed. The lower rate of OPG/sRANKL reduction in the n-3-enriched PLE group indicates that n-3 PUFA-enriched PLEs may help to attenuate early bone loss in VLBW neonates.

Modifications of Own Mothers' Milk Fortification Protocol Affect Early Plasma IGF-I and Ghrelin Levels in Preterm Infants. A Randomized Clinical Trial.

The aim was to investigate the effect of two own mother's milk (OMM) fortification protocols on (a) IGF-I and ghrelin plasma levels at 35 post-conceptional weeks (PCW, T2) and whether this effect is maintained after elimination of the differences in OMM fortification, and (b) growth until 12 months corrected age. Forty-eight OMM-fed preterm infants (GA 24-32 weeks) were randomly allocated to the fixed-fortification (FF) group (n = 23) and the protein-targeting fortification (PTF) group (n = 25) targeting the recommended daily protein intake (PI). Plasma IGF-I and ghrelin were assessed at 35 (T2) and 40 (T3) PCW while growth was longitudinally assessed until 12 months corrected age. PTF group had lower IGF-I and higher ghrelin than FF group at T2, while receiving lower daily protein and energy amounts. PI correlated positively to T2-IGF-I and inversely to T3-ghrelin while energy intake (EI) correlated inversely to T2- and T3-ghrelin. Group and PI were independent predictors of adjusted T2-IGF-I, while group and EI were predictors of adjusted and T2-ghrelin. Growth parameter z-scores were comparable between groups up to 12 months corrected age. Modifications of OMM fortification have a transient effect on early plasma IGF-I and ghrelin levels in preterm infants in a way consistent with the previously recognized protein-energy/endocrine balance, indicating a potential programming effect.

Mediterranean Diet Adherence is Associated with Lower Prevalence of Functional Gastrointestinal Disorders in Children and Adolescents.

Dietary patterns may have a role in the prevention of functional gastrointestinal disorders (FGIDs). The current study aimed at examining the association between FGIDs and adherence to the Mediterranean diet (MD) among elementary school children (ESC), as well as high school students (HSS). In a prospective cohort study, data from 1116 subjects (387 ESC and 448 HSS) aged 6-18 years were collected. FGID identification was based on the Questionnaire on Pediatric Gastrointestinal Symptoms-Rome III (QPGS-RIII). Adherence to the MD was assessed using the KIDMED Index. Full data were available on 835/1116 questionnaires. Based on Rome III criteria, 184/835 participants (22%) were identified with FGID (122 (66%) with functional constipation (FC)). The prevalence of FGIDs (p = 0.001) was significantly higher in HSS (13-18 years). The KIDMED score in the cohort was 5.7 ± 2.5. Subjects with FGIDs demonstrated a lower KIDMED score compared to the non-FGID group, both in the cohort, as well as in the ESC and HSS subgroups (FGID vs. non-FGID: p = 0.001, p = 0.007, and p = 0.032, respectively). Multivariate analysis highlighted the KIDMED score as a significant predictor of FGIDs and FC after controlling for the age subgroups. We conclude that good adherence to the MD is associated to lower prevalence of FGIDs, while adolescents display a significantly higher prevalence of FGIDs compared to children.

A pilot case-control study of urine metabolomics in preterm neonates with necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is a leading cause of gastrointestinal morbidity and mortality in preterm neonates. The aim of this pilot study was to explore using metabolomics alternations in the urine metabolites related to NEC that could possibly serve as diagnostic biomarkers of the disease. Urine samples were prospectively collected at the day of initial evaluation for NEC from 15 diseased preterm neonates (five Bell's stage I and ten stage II/III) and an equal number of matched controls. Urine metabolic profiles were assessed using non-targeted nuclear magnetic resonance spectroscopy and targeted liquid chromatography-tandem mass spectrometry monitoring 108 metabolites. Multivariate statistical models with data from either analytical approach showed clear separation between the metabolic profiles of neonates with NEC and controls. Twenty-five discriminant metabolites were identified belonging to amino and organic acids, sugars and vitamins. A number of metabolite combinations were found to have an excellent diagnostic performance in detecting neonates developing NEC. Our results show that the metabolic profile of neonates with NEC differs significantly from that of controls, making possible their separation using urine metabolomic analysis. Nevertheless, whether the small set of significant metabolites detected in this investigation could be used as early diagnostic biomarkers of NEC should be validated in larger studies.

Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-Linked Syndrome Associated With a Novel Mutation of FOXP3 Gene.

The immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare, x-linked, recessive disorder characterized by dysfunction of the T regulatory (Treg) lymphocytes leading to autoimmune diseases. Herein we report a male patient with IPEX syndrome who presented with severe diarrhea, eczema, and malabsorption leading to failure to thrive and necessitating total parenteral nutrition, as well as with liver dysfunction. Laboratory investigation showed elevated liver enzymes that declined following treatment with glucocorticosteroids and immunosuppressive drugs, marked eosinophilia, increased total IgE, and decreased Treg cells. DNA analysis revealed that the patient himself was hemizygous and his mother heterozygous for the exon 10, c.1015C>T (p.Pro339Ser) mutation of the FOXP3 gene, which has not been previously reported. The current case indicates that mutations resulting in substitution of a certain amino-acid (i.e., proline 339) by different amino-acids are manifested with different IPEX phenotypes.

The Mediterranean diet adherence by pregnant women delivering prematurely: association with size at birth and complications of prematurity.

Background: The Mediterranean diet (MD) is associated with decreased risk of metabolic syndrome and gestational diabetes due to the anti-inflammatory and antioxidative properties of its components. The aim was to investigate the potential association of MD adherence (MDA) during pregnancy by mothers delivering prematurely, with intrauterine growth as expressed by neonates' anthropometry at birth and complications of prematurity. Participants and methods: This is a single-center, prospective, observational cohort study of 82 women who delivered preterm singletons at post conceptional age (PCA) ≤ 34 weeks and their live-born neonates. Maternal and neonatal demographic and clinical data were recorded. All mothers filled in a food frequency questionnaire, and the MDA score was calculated. Based on 50th centile of MD score, participants were classified into high-MDA and low-MDA groups. Results: The low-MDA mothers had significantly higher pregestational BMI and rates of overweight/obesity (odd ratios (OR) 3.5) and gestational hypertension/preeclampsia (OR 3.8). Neonates in the low-MDA group had significantly higher incidence of intrauterine growth restriction (IUGR) (OR 3.3) and lower z-scores of birth weight and BMI. Regarding prematurity-related complications, the low MDA-group was more likely to develop necrotizing enterocolitis, bronchopulmonary dysplasia, and retinopathy of prematurity (OR 3.2, 1.3, and 1.6, respectively), while they were less likely to develop respiratory distress syndrome (OR 0.49), although the differences were not statistically significant. However, adjustment for confounders revealed MDA as a significant independent predictor of hypertension/preeclampsia, IUGR, birth weight z-score, necrotizing enterocolitis, and bronchopulmonary dysplasia. Conclusions: High MDA during pregnancy may favorably affect intrauterine growth and certain acute and chronic complications of prematurity as well as maternal hypertension/preeclampsia.

Targeted LC-MS/MS for the evaluation of proteomics biomarkers in the blood of neonates with necrotizing enterocolitis and late-onset sepsis.

Late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) are severe life-threatening conditions for neonates. Accurate, early diagnosis and timely initiation of treatment are crucial. Non-specific overlapping clinical signs along with the non-sensitive/specific diagnostic tools set obstacles to speedy, trustful diagnosis including differential diagnosis. The objective of this study was to evaluate the potential of targeted LC-MS/MS proteomics in identifying diagnostic biomarkers of NEC or LOS. We conducted a prospective case-control study evaluating serum proteomics profiles of 25 NEC, 18 LOS, and an equal number of matched control neonates, over three sampling points. Eighty-three concatemers and synthetic peptides belonging to 47 protein markers of the two diseases were selected after thorough literature search. A novel selected reaction monitoring (SRM), LC-MS/MS method was developed for their analysis and evaluation as potential biomarkers. Multivariate and univariate statistical analyses highlighted significant proteins in differentiating LOS and NEC neonates and diseased from controls. Moreover, panels of proteins were tested for their ability to distinguish LOS from NEC and controls. We suggest two panels of three proteins each, exhibiting very high diagnostic value for LOS and excellent diagnostic performance at the critical LOS-NEC differentiation, reaching an AUC ROC value close to 1 (0.999). These panels constitute a valuable starting point for further validation with broader cohorts of neonates, aiming to improve the clinical practice. Graphical abstract ᅟ.

Anthropometry and Body Composition of Preterm Neonates in the Light of Metabolic Programming.

The improved survival of preterm infants has led to increased interest regarding their health as adults. In the context of metabolic programming, the connection between perinatal and early postnatal nutrition and growth with health in later life has brought to the fore the role of catch-up growth during the first months of preterm infants' lives and its association with body fat and obesity in childhood or puberty. A state-of-the art review was conducted in order to assess the way catch-up is evaluated, in terms of timing and rate. Adequate growth is of major importance for neurodevelopment; however, it may compete with adiposity or metabolic health. Studies based on body composition assessment have given conflicting results as regards the effect of early versus late and rapid versus slow catch-up growth on later health, mainly attributed to the lack of established criteria and definitions. Given that adequate early nutrition is crucial for the neurodevelopment of preterm infants, further studies are needed on the role of catch-up growth in long-term outcome, using generally accepted qualitative and quantitative criteria.

Urine metabolomics in neonates with late-onset sepsis in a case-control study.

Although late-onset sepsis (LOS) is a major cause of neonatal morbidity and mortality, biomarkers evaluated in LOS lack high diagnostic accuracy. In this prospective, case-control, pilot study, we aimed to determine the metabolic profile of neonates with LOS. Urine samples were collected at the day of initial LOS evaluation, the 3rd and 10th day, thereafter, from 16 septic neonates (9 confirmed and 7 possible LOS cases) and 16 non-septic ones (controls) at respective time points. Urine metabolic profiles were assessed using non-targeted nuclear magnetic resonance spectroscopy and targeted liquid chromatography-tandem mass spectrometry analysis. Multivariate statistical models with data from either analytical approach showed clear separation between the metabolic profiles of septic neonates (both possible and confirmed) and the controls. Metabolic changes appeared to be related to disease progression. Overall, neonates with confirmed or possible LOS exhibited comparable metabolic profiles indicating similar metabolic alternations upon the onset of clinical manifestations. This methodology therefore enabled the discrimination of neonates with LOS from non-septic individuals, providing potential for further research toward the discovery of LOS-related biomarkers.

Parenteral MCT/ω-3 Polyunsaturated Fatty Acid-Enriched Intravenous Fat Emulsion Is Associated With Cytokine and Fatty Acid Profiles Consistent With Attenuated Inflammatory Response in Preterm Neonates: A Randomized, Double-Blind Clinical Trial.

BACKGROUND: Soybean oil-based intravenous fat emulsion (IVFE) administered to preterm neonates can induce oxidative stress and inflammatory response, which are associated with severe complications of prematurity. This study aimed to test the hypothesis that administration of medium-chain triglyceride (MCT)/ω-3 polyunsaturated fatty acid (PUFA)-enriched IVFE in preterm neonates is associated with a cytokine and fatty acid (FA) profile consistent with attenuated inflammatory response. PATIENTS/METHODS: In a double-blind randomized study, 60 preterm neonates (gestational age 26-32 weeks) were randomized to receive either MCT/ω-3 PUFA-enriched IVFE (intervention group) or soybean oil-based IVFE (control group). Serum biochemistry, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-8, α-tocopherol, and FAs were assessed at baseline, on day of life 15, and day of life 30 or at the end of intervention. RESULTS: All cytokine levels changed significantly across the 3 time points, whereas the type of IVFE had a significant effect on final IL-6 and IL-8 levels, which were lower in the intervention group. The difference in final IL-6 and IL-8 levels remained significant after controlling for bronchopulmonary dysplasia and/or infection. α-Tocopherol and FA values changed significantly over time. MCT/ω-3 PUFA-enriched IVFE administration was associated with significantly higher α-tocopherol, eicosapentaenoic acid, docosahexaenoic acid, and ω-3 PUFAs and lower linolenic acid, total PUFA, and ω-6/ω-3 PUFA values compared with soybean oil-based IVFE. Both IVFEs were well tolerated. CONCLUSION: Compared with the soybean oil-based IVFE, the MCT/ω-3 PUFA-enriched IVFE is associated with a more favorable cytokine and FA profile consistent with attenuated inflammatory response in preterm neonates.

Computer-based malnutrition risk calculation may enhance the ability to identify pediatric patients at malnutrition-related risk for unfavorable outcome.

BACKGROUND: The study aimed to test the hypothesis that computer-based calculation of malnutrition risk may enhance the ability to identify pediatric patients at malnutrition-related risk for an unfavorable outcome. The Pediatric Digital Scaled MAlnutrition Risk screening Tool (PeDiSMART), incorporating the World Health Organization (WHO) growth reference data and malnutrition-related parameters, was used. MATERIALS AND METHODS: This was a prospective cohort study of 500 pediatric patients aged 1 month to 17 years. Upon admission, the PeDiSMART score was calculated and anthropometry was performed. Pediatric Yorkhill Malnutrition Score (PYMS), Screening Tool Risk on Nutritional Status and Growth (STRONGkids), and Screening Tool for the Assessment of Malnutrition in Pediatrics (STAMP) malnutrition screening tools were also applied. PeDiSMART's association with the clinical outcome measures (weight loss/nutrition support and hospitalization duration) was assessed and compared with the other screening tools. RESULTS: The PeDiSMART score was inversely correlated with anthropometry and bioelectrical impedance phase angle (BIA PhA). The score's grading scale was based on BIA Pha quartiles. Weight loss/nutrition support during hospitalization was significantly independently associated with the malnutrition risk group allocation on admission, after controlling for anthropometric parameters and age. Receiver operating characteristic curve analysis showed a sensitivity of 87% and a specificity of 75% and a significant area under the curve, which differed significantly from that of STRONGkids and STAMP. In the subgroups of patients with PeDiSMART-based risk allocation different from that based on the other tools, PeDiSMART allocation was more closely related to outcome measures. CONCLUSION: PeDiSMART, applicable to the full age range of patients hospitalized in pediatric departments, graded according to BIA PhA, and embeddable in medical electronic records, enhances efficacy and reproducibility in identifying pediatric patients at malnutrition-related risk for an unfavorable outcome. Patient allocation according to the PeDiSMART score on admission is associated with clinical outcome measures.

Cholestasis, bronchopulmonary dysplasia, and lipid profile in preterm infants receiving MCT/ω-3-PUFA-containing or soybean-based lipid emulsions.

BACKGROUND: This study aimed to compare the effect of 2 lipid emulsions (LEs), a medium-chain triglyceride (MCT)/ω-3-polyunsaturated fatty acid (PUFA)-containing LE and a soybean-based LE, on the incidence of neonatal cholestasis, bronchopulmonary dysplasia (BPD), and lipid profile of preterm infants. Patients and METHODS: In this prospective, observational study, 2 groups of preterm neonates, the very low birth weight (VLBW) (n = 129) and the low birth weight (LBW) groups (n = 153), which received parenteral LEs for at least 7 days, were included. Infants received either MCT/ω-3-PUFA-containing LE (SMOFlipid, subgroup I) or soybean-based LE (Intralipid, subgroup II) according to the attending neonatologist's preference and availability. Full biochemical assessment was performed on days of life 15, 30, and 45 and on discharge. RESULTS: Of the VLBW infants, 7.4% and 13.3% of infants in subgroups I and II, respectively, developed cholestasis (P = .39; odds ratio [OR], 0.52; 95% confidence interval [CI], 0.15-1.76). The duration of LE administration was independently associated with cholestasis (P < .001; OR, 0.925; 95% CI, 0.888-0.963). The maximum amounts of lipids administered ranged between 1.6 and 3.6 g/kg/d in both VLBW subgroups. The VLBW subgroup I had lower incidence of BPD, lower alkaline phosphatase and phosphate, higher high-density lipoprotein (HDL), and lower cholesterol-to-HDL ratio on discharge than the VLBW subgroup II. The type of LE was independently associated with BPD and alkaline phosphatase. In the LBW group, the type of LE was not associated with clinical and biochemical parameters. CONCLUSION: In VLBW infants, the MCT/ω-3-PUFA-containing LE administration is associated with decreased BPD and more favorable lipoprotein profile. Although a trend toward a lower incidence of cholestasis was observed, a preventive effect of MCT/ω-3-PUFA-containing LE on parenteral nutrition-associated cholestasis is not supported.