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Limited prospective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) data in children regarding the impact of Omicron variant in seropositivity have been reported. We investigated SARS-CoV-2 seropositivity in children between 1 September 2021 and 30 April 2022, representing Delta and Omicron predominance periods. Serum samples from children admitted to the major tertiary Greek paediatric hospital for any cause, except for COVID-19, were randomly collected and tested for SARS-CoV-2 natural infection antibodies against nucleocapsid antigen (Elecsys® Anti-SARS-CoV-2 reagent). A total of 506/1312 (38.6%) seropositive children (0–16 years) were detected (males: 261/506(51.6%); median age (IQR): 95.2 months(24–144)). Seropositivity rates (%) increased from Delta to Omicron period from 29.7% to 48.5% (P-valueP-value:0.914). The highest seropositivity rate was detected in April 2022 (52.6%) and reached 73.9% specifically for the age group 12–16 years. No significant differences were detected in seropositivity with respect to gender, origin, or hospitalisation status. Median (IQR) antibody titres were higher in the Omicron vs. Delta period in all age groups, especially in 12–16 years [32.2 COI (7–77.1) vs. 11.4 COI(2.8–50.2), P-value:0.009). During Omicron variant period increased SARS-CoV-2 seropositivity was detected in paediatric population, especially in adolescents, implicating either increased transmissibility or reinfection rates.

BACKGROUND Endothelial microparticles (EMPs) act as early biomarkers of endothelial activation and damage. No studies have investigated EMPs in preterm-born individuals. METHODS Sixty-three preterm-born children and 52 children born full-term (controls) were studied. Circulating CD62E(+), CD144(+), and CD31(+)/CD42b(-) EMPs were measured in preterm-born children compared to controls; possible associations with cardiovascular risk factors and endothelial function parameters were also assessed. RESULTS Circulating CD62E(+), CD144(+), and CD31(+)/CD42b(-) EMPs were significantly higher in preterm-born children compared to controls (p = 0.003, p

Introduction: Prematurity is associated with increased cardiometabolic risk later in life. The adipomyokine irisin has been acknowledged as a modulator of energy metabolism and insulin sensitivity. The aim of this study was to investigate circulating levels of irisin and their relation to anthropometric measurements and cardiometabolic phenotype in a population of preterm-born children versus full-term-born peers. Methods: A total of 160 children (87 born preterm aged 8.1–14.8 years and 73 born full-term of similar age and gender distribution) were studied. Arterial blood pressure, anthropometry, body composition assessments with dual energy X-ray absorptiometry, and skinfold measurements were performed. Blood biochemistry and circulating levels of irisin, insulin, cortisol, leptin, and adiponectin were also determined. Results: The preterm group had higher diastolic blood pressure, triceps skinfold, subscapular skinfold (SSSF), and abdominal skinfold measurements and more central adiposity than the full-term group. Irisin was significantly lower (p = 0.002), whereas leptin was higher (p = 0.03) in the preterm than the full-term group. Irisin correlated positively with gestational age (r = 0.19, p = 0.01), birth weight (r = 0.23, p = 0.003), and high-density lipoprotein cholesterol (r = 0.20, p = 0.01) and negatively with SSSF (r = −0.25, p = 0.003) and chronological age (r = −0.21, p = 0.008). Conclusion: Lower levels of irisin and a slightly unhealthy adiposity and cardiometabolic pattern were detected in preterm-born children in comparison to their full-term-born peers. Whether low irisin levels in preadolescents and adolescents born prematurely could be of prognostic value for the development of cardiometabolic sequelae later in life remains to be further studied.

BACKGROUND Endothelial progenitor cells (EPCs) ensure vascular integrity and neovascularization. No studies have investigated EPCs in preterm-born children beyond infancy. METHODS One hundred and thirty-six prepubertal children were enrolled: 63 preterm and 73 born at term (controls). Circulating CD34(+)/VEGFR-2(+)/CD45(-) and CD34(+)/VEGFR-2(+)/CD45dim EPCs were measured in preterm-born children compared to controls. Body mass index (BMI), waist-to-hip ratio (WHR), neck circumference, systolic and diastolic blood pressure (SBP and DBP, respectively), fasting glucose, insulin, lipid profile, common carotid and abdominal aortic intima-media thickness (cIMT and aIMT, respectively), endothelium-dependent brachial artery flow-mediated dilation (FMD), and echocardiographic parameters were also assessed. RESULTS Circulating CD34(+)/VEGFR-2(+)/CD45(-) and CD34(+)/VEGFR-2(+)/CD45dim EPCs were significantly higher in preterm-born children compared to controls (p

Combined pituitary hormone deficiency (CPHD) is characterized by deficiency of growth hormone and at least one other pituitary hormone. Pathogenic variants in more than 30 genes expressed during the development of the head, hypothalamus, and/or pituitary have been identified so far to cause genetic forms of CPHD. However, the etiology of around 85% of the cases remains unknown. The aim of this study was to unveil the genetic etiology of CPHD due to congenital hypopituitarism employing whole exome sequencing (WES) in two newborn patients, initially tested and found to be negative for PROP1, LHX3, LHX4 and HESX1 pathogenic variants by Sanger sequencing and for copy number variations by MLPA. In this study, the application of WES in these CPHD newborns revealed the presence of three different heterozygous gene variants in each patient. Specifically in patient 1, the variants BMP4; p.Ala42Pro, GNRH1; p.Arg73Ter and SRA1; p.Gln32Glu, and in patient 2, the SOX9; p.Val95Ile, HS6ST1; p.Arg306Gln, and IL17RD; p.Pro566Ser were identified as candidate gene variants. These findings further support the hypothesis that CPHD constitutes an oligogenic rather than a monogenic disease and that there is a genetic overlap between CPHD and congenital hypogonadotropic hypogonadism.

BACKGROUND To evaluate the performance of serum amyloid-A (SAA), high-density lipoprotein cholesterol (HDL-C) and apolipoprotein-A1 (Apo-A1) levels in the identification and monitoring of neonatal sepsis. METHODS This prospective study included 113 full-term septic neonates (postnatal age 4-28 days) admitted to the Special Care Neonatal Unit of a University Hospital from January 1, 2016, to April 30, 2019, and 68 healthy neonates (controls). Blood samples were drawn serially in septic neonates at enrollment and on days 1, 3 and 7, and once in controls, for SAA, HDL-C and Apo-A1 determination. RESULTS At enrollment, SAA levels were significantly higher in septic neonates in comparison with controls (median 50.7 vs. 3.5 mg/L; P < 0.0001); HDL-C and Apo-A1 levels were significantly lower in patients than in controls (P < 0.001 and P < 0.006, respectively). SAA levels were higher in culture-positive compared with culture-negative sepsis (median 202.0 vs. 14.2 mg/L; P < 0.0001). HDL-C and Apo-A1 levels did not differ significantly between culture-positive and culture-negative sepsis. Receiver operating characteristic curve analysis of SAA levels at enrollment resulted in significant areas under the curve (AUC) for detecting sepsis {AUC = 0.929 [95% confidence interval: 0.885-0.973]; P < 0.0001} and also for discriminating between culture-positive and culture-negative sepsis [AUC = 0.933 (95% confidence interval: 0.882-0.984); P < 0.0001]. The combination of HDL-C and Apo-A1 with SAA increased its diagnostic performance. Furthermore, serial SAA levels following enrollment could indicate clinical response in septic neonates. CONCLUSIONS SAA seems to be a useful biomarker for identification and monitoring of neonatal sepsis, and also for discriminating between culture-positive and culture-negative sepsis. HDL-C and Apo-A1 could be used as complementary markers.

Summary Background Vancomycin is the most widely used antibiotic for neonatal Gram-positive sepsis, but clinical outcome data of dosing strategies are scarce. The NeoVanc programme comprised extensive preclinical studies to inform a randomised controlled trial to assess optimised vancomycin dosing. We compared the efficacy of an optimised regimen to a standard regimen in infants with late onset sepsis that was known or suspected to be caused by Gram-positive microorganisms. Methods NeoVanc was an open-label, multicentre, phase 2b, parallel-group, randomised, non-inferiority trial comparing the efficacy and toxicity of an optimised regimen of vancomycin to a standard regimen in infants aged 90 days or younger. Infants with at least three clinical or laboratory sepsis criteria or confirmed Gram-positive sepsis with at least one clinical or laboratory criterion were enrolled from 22 neonatal intensive care units in Greece, Italy, Estonia, Spain, and the UK. Infants were randomly assigned (1:1) to either the optimised regimen (25 mg/kg loading dose, followed by 15 mg/kg every 12 h or 8 h dependent on postmenstrual age, for 5 ± 1 days) or the standard regimen (no loading dose; 15 mg/kg every 24 h, 12 h, or 8 h dependent on postmenstrual age for 10 ± 2 days). Vancomycin was administered intravenously via 60 min infusion. Group allocation was not masked to local investigators or parents. The primary endpoint was success at the test of cure visit (10 ± 1 days after the end of actual vancomycin therapy) in the per-protocol population, where success was defined as the participant being alive at the test of cure visit, having a successful outcome at the end of actual vancomycin therapy, and not having a clinically or microbiologically significant relapse or new infection requiring antistaphylococcal antibiotics for more than 24 h within 10 days of the end of actual vancomycin therapy. The non-inferiority margin was −10%. Safety was assessed in the intention-to-treat population. This trial is registered at ClinicalTrials.gov ( NCT02790996 ). Findings Between March 3, 2017, and July 29, 2019, 242 infants were randomly assigned to the standard regimen group (n=122) or the optimised regimen group (n=120). Primary outcome data in the per-protocol population were available for 90 infants in the optimised group and 92 in the standard group. 64 (71%) of 90 infants in the optimised group and 73 (79%) of 92 in the standard group had success at test of cure visit; non-inferiority was not confirmed (adjusted risk difference −7% [95% CI −15 to 2]). Incomplete resolution of clinical or laboratory signs after 5 ± 1 days of vancomycin therapy was the main factor contributing to clinical failure in the optimised group. Abnormal hearing test results were recorded in 25 (30%) of 84 infants in the optimised group and 12 (15%) of 79 in the standard group (adjusted risk ratio 1·96 [95% CI 1·07 to 3·59], p=0·030). There were six vancomycin-related adverse events in the optimised group (one serious adverse event) and four in the standard group (two serious adverse events). 11 infants in the intention-to-treat population died (six [6%] of 102 infants in the optimised group and five [5%] of 98 in the standard group). Interpretation In the largest neonatal vancomycin efficacy trial yet conducted, no clear clinical impact of a shorter duration of treatment with a loading dose was demonstrated. The use of the optimised regimen cannot be recommended because a potential hearing safety signal was identified; long-term follow-up is being done. These results emphasise the importance of robust clinical safety assessments of novel antibiotic dosing regimens in infants. Funding EU Seventh Framework Programme for research, technological development and demonstration.

Breast milk is the ideal food for infants and undoubtedly has immediate and long‑term benefits. Breast milk contains extracellular vesicles (EVs) i.e., exosomes secreted by maternal breast cells. Exosomes carry genetic material, such as long non‑coding RNAs (lncRNAs), which possibly participate in cell‑to‑cell communications, as they are known to regulate critical gene pathways. The aim of the present study was to screen human breastmilk exosomes for their lncRNA cargo and to examine exosomal lncRNA levels associated with milk obtained from mothers that gave birth at term or prematurely (

Background Neonatal respiratory distress syndrome (NRDS) is strongly associated with premature birth, but it can also affect term neonates. Unlike the extent of research in preterm neonates, risk factors associated with incidence and severity of NRDS in term neonates are not well studied. In this study, we examined the association of maternal and neonatal risk factors with the incidence and severity of NRDS in term neonates admitted to Neonatal Intensive Care Unit (NICU) in Cyprus. Methods In a prospective, case-control design we recruited term neonates with NRDS and non-NRDS admitted to the NICU of Archbishop Makarios III hospital, the only neonatal tertiary centre in Cyprus, between April 2017–October 2018. Clinical data were obtained from patients’ files. We used univariate and multivariate logistic and linear regression models to analyse binary and continuous outcomes respectively. Results During the 18-month study period, 134 term neonates admitted to NICU were recruited, 55 (41%) with NRDS diagnosis and 79 with non-NRDS as controls. In multivariate adjusted analysis, male gender (OR: 4.35, 95% CI: 1.03–18.39, p = 0.045) and elective caesarean section (OR: 11.92, 95% CI: 1.80–78.95, p = 0.01) were identified as independent predictors of NRDS. Among neonates with NRDS, early-onset infection tended to be associated with increased administration of surfactant (β:0.75, 95% CI: − 0.02-1.52, p = 0.055). Incidence of pulmonary hypertension or systemic hypotension were associated with longer duration of parenteral nutrition (pulmonary hypertension: 11Vs 5 days, p p = 0.01) and higher rate of blood transfusion (pulmonary hypertension: 100% Vs 67%, p = 0.045, systemic hypotension: 85% Vs 55%, p = 0.013). Conclusions This study highlights the role of elective caesarean section and male gender as independent risk factors for NRDS in term neonates. Certain therapeutic interventions are associated with complications during the course of disease. These findings can inform the development of evidence-based recommendations for improved perinatal care.

Background and objectives: Parenteral nutrition (PN) is an integral part of the nutritional support of critically ill neonates in the intensive care units (ICU). The evaluation of a decision support system for total nutrients (DSSFTN) is of great importance for clinical practice. This study’s aim was to evaluate the impact caused by implementation of a DSSFTN on PN support and neonatal growth. This pilot work was supported by the hospital PN team (PNT) in order to assess possible benefits stemming from the use of DSSFTN. Materials and methods: DSSFTN development is based on the incorporation of pharmaceutical and therapeutic protocols. Thirty-eight neonates were recruited. Inclusion criteria included: patients should (a) be hospitalized in ICU, (b) receive PN support at least for 15 days, (c) have birth weight 550–1600 g. One exclusion criterion was applied: patients should have no inborn error of metabolism. 15 doctors prescribed PN for two groups of neonates. PN was calculated by doctors for Group 1 (19 neonates) and respectively was calculated by the DSSFTN (and checked by doctors) for Group 2 (19 neonates). A questionnaire was completed later by doctors to evaluate DSSFTN. Results: The implementation of DSSFTN led to appropriate composition and administration of PN. Growth was not significantly different between the study groups. Compliance with guidelines was observed. DSSFTN ameliorated intercommunication among doctors. Conclusions: The implementation of DSSFTN enables health professionals to facilitate the complex task of prescribing. It ensures the consistency of PN prescriptions, as it leads to appropriate dosing in all nutrients. DSSFTN provides real-time PN interventions (clinical conditions and enteral amounts are included additionally) and minimizes exposure to human errors.

Background A rare disorder of sex development is 45,X/46,XY mosaicism, which is phenotypically very heterogenous, ranging from normal male (or female) to that of genital ambiguity of varying degrees. Case We report a case of a neonate with 45,X/46,XY mosaicism and hydrocolpos, and we point out the dilemma and the difficulty in gender assignment. Summary and Conclusion Gender assignment of cases with frank genital ambiguity is often difficult to be determined, because several factors have to be taken into consideration, such as genital appearance, anticipated urological and sexual function, capacity for future fertility, gonadal malignancy risk, and psychosocial factors. A multidisciplinary approach is definitely needed in the management of such cases.

Aim: To validate the Greek version of Kennerley and Gath’s Blues Questionnaire (BQ) and gather further knowledge on maternity blues (MB) associations with certain clinical and sociodemographic fact...

Limited recent molecular epidemiology data are available for pediatric Central Nervous System (CNS) infections in Europe. The aim of this study was to investigate the molecular epidemiology of enterovirus (EV) involved in CNS infections in children. Cerebrospinal fluid (CSF) from children (0&ndash, 16 years) with suspected meningitis&ndash, encephalitis (ME) who were hospitalized in the largest pediatric hospital of Greece from October 2017 to September 2020 was initially tested for 14 common pathogens using the multiplex PCR FilmArray&reg, ME Panel (FA-ME). CSF samples positive for EV, as well as pharyngeal swabs and stools of the same children, were further genotyped employing Sanger sequencing. Of the 330 children tested with FA-ME, 75 (22.7%) were positive for EV and 50 different CSF samples were available for genotyping. The median age of children with EV CNS infection was 2 months (IQR: 1&ndash, 60) and 44/75 (58.7%) of them were male. There was a seasonal distribution of EV CNS infections, with most cases detected between June and September (38/75, 50.7%). EV genotyping was successfully processed in 84/104 samples: CSF (n = 45/50), pharyngeal swabs (n = 15/29) and stools (n = 24/25). Predominant EV genotypes were CV-B5 (16/45, 35.6%), E30 (10/45, 22.2%), E16 (6/45, 13.3%) and E11 (5/45, 11.1%). However, significant phylogenetic differences from previous described isolates were detected. No unusual neurologic manifestations were observed, and all children recovered without obvious acute sequelae. Specific EV circulating genotypes are causing a significant number of pediatric CNS infections. Phylogenetic analysis of these predominant genotypes found genetic differences from already described EV isolates.

Background and aimA measles outbreak occurred in Greece during 2017–2018 affecting mainly pediatric population. The aim of the study was to describe the epidemiological and clinical characteristics of the cases diagnosed in the major pediatric tertiary hospital of Athens, where 26.5% of national pediatric measles cases were diagnosed and treated.MethodsThis is a retrospective study of children 0–16 years old, who presented at the emergency department and/or were hospitalized with clinical presentation compatible with measles and diagnosis was confirmed with molecular detection of the measles RNA in pharyngeal swabs. Epidemiological, clinical and laboratory characteristics were retrieved from medical records and analyzed.ResultsA total of 578 children with measles were identified during the study period. 322 (55.7%) were male with median age 36 months (range:1–193), while the largest number of documented cases (251; 43.4%) were children aged 1–5 years. Most children (429/578; 74.2%) belonged to the Roma minority and only 64 (11.1%) had Greek origin. 497 (91.5%) children were unvaccinated and 37 (6.8%) were partially vaccinated with measles vaccine. Hospitalization was required for 342 (59.2%) children, whereas one or more complications were reported in 230 (67.2%) of them. Most frequent complications were elevated transaminases (139; 40.6%), acute otitis media (72; 21%), dehydration (67; 19.6%) and pneumonia (58; 16.9%). 11 children (3.2%) required intensive care admission for altered mental status/status epilepticus (3), sepsis (2) and ARDS (6). 119/342 (34.8%) children were treated with antibiotics because of possible or confirmed bacterial coinfection. One death was reported, concerning an 11-month-old unvaccinated infant, with underlying dystrophy, who died of sepsis.ConclusionMeasles is not an innocent viral infection, as it is still characterized by high morbidity and complications rates. Unvaccinated or partially vaccinated populations could trigger new outbreaks, resulting in significant cost in public health. To avoid future measles outbreaks, high vaccination coverage should be achieved, as well as closing immunity gaps in the population and ensuring high-quality measles surveillance.

Intravenous administration of pure soybean oil emulsions high in linoleic acid may lead to inflammation and lipid peroxidation in preterm neonates. We aimed to investigate the effects of a medium-chain triglyceride (MCT)/&omega, 3 polyunsaturated fatty acid (PUFA)-enriched intravenous fat emulsion (IVFE) on plasma fatty acid (FA) profile and serum interleukin-6 (IL-6) in preterm neonates. In this double-blind randomized study, 92 preterm neonates (gestational age &lt, 32 weeks, birth weight &lt, 1500 g) were assigned to receive either MCT/&omega, 3 PUFA-enriched IVFE (Intervention Group) or soybean oil-based IVFE (Control Group). Levels of FAs were measured at baseline (day 0) and day 15 of parenteral nutrition with gas-chromatography mass-spectrometry. Serum IL-6 was measured with sandwich ELISA in 59 neonates. Plasma FAs changed significantly over time, the MCT/&omega, 3 PUFA-IVFE group showed higher &omega, 3 PUFAs (p = 0.031), eicosapentaenoic acid (p = 0.000), and oleic acid (p = 0.003), and lower &omega, 6/&omega, 3 PUFAs ratio (p = 0.001) and &omega, 6 PUFAs (p = 0.023) compared to control group. Linoleic acid was higher in the soybean oil (SO)-based IVFE arm compared to the MCT/&omega, 3 PUFAs-IVFE arm (p = 0.006). Both fat emulsion types decreased IL-6 compared to baseline, but changes were insignificant between groups. Administration of MCT/&omega, 3 PUFA-enriched IVFE in preterm neonates is beneficial in changing the FA profile consistent with attenuated inflammatory response.

Despite improvements in viability, the long-term neurodevelopmental outcomes of preterm babies remain serious concern as a significant percentage of these infants develop neurological and/or intellectual impairment, and they are also at increased risk of psychiatric illnesses later in life. The current challenge is to develop neuroprotective approaches to improve adverse outcomes in preterm survivors. The purpose of this review was to provide an overview of the current evidence on pharmacological agents targeting the neuroprotection of the preterm brain. Among them, magnesium sulfate, given antenatally to pregnant women with imminent preterm birth before 30 to 34 weeks of gestation, as well as caffeine administered to preterm infants after birth, exhibited neuroprotective effects for human preterm brain. Erythropoietin treatment of preterm infants did not result in neuroprotection at 2 years of age in two out of three published large randomized controlled trials; however, long-term follow-up of these infants is needed to come to definite conclusions. Further studies are also required to assess whether melatonin, neurosteroids, inhaled nitric oxide, allopurinol, or dietary supplements (omega-3 fatty acids, choline, curcumin, etc.) could be implemented as neuroprotectants in clinical practice. Furthermore, other pharmacological agents showing promising signs of neuroprotective efficacy in preclinical studies (growth factors, hyaluronidase inhibitors or treatment, antidiabetic drugs, cannabidiol, histamine-H3 receptor antagonists, etc.), as well as stem cell- or exosomal-based therapies and nanomedicine, may prove useful in the future as potential neuroprotective approaches for human preterm brain. KEY POINTS: · Magnesium and caffeine have neuroprotective effects for the preterm brain.. · Follow-up of infants treated with erythropoietin is needed.. · Neuroprotective efficacy of several drugs in animals needs to be shown in humans..

The aim of the study was to evaluate the impact of the use of BioFire® FilmArray® meningitis/encephalitis(FA-ME) panel which enables rapid automated CSF testing for 14 common viral, bacterial, and yeast pathogens that cause CNS infections, in the management of children with suspected CNS infection. A prospective cohort study was performed on children admitted to a tertiary pediatric hospital, over a period of 1 year, with possible CNS infection and CSF pleocytosis (> 15 cells/mm3). Children were randomized 1:1, either to use FA-ME or separate molecular CSF microbiological tests according to usual pediatric practice in the hospital. Length of hospital stay, duration of antimicrobials, and total cost of hospitalization were compared between groups. A total of 142 children were included in the study (71 cases). A pathogen was detected in 37/71(52.1%) children with the use of FA-ME and in 16/71(22.5%) in the control group (P value

Two-dimensional (2-D) shear wave elastography is a new sonographic elastography method for noninvasive measurement of liver stiffness. The aim of this study was to establish reference values of normal liver stiffness on 2-D shear wave elastography in children. Two-dimensional shear wave elastography values were measured in 202 children with no liver disease from the neonatal period to puberty, who were divided into 4 age groups: newborns and infants, preschoolers, elementary school children and adolescents. We investigated the effects of age, depth of elastography measurement, transducer, number of measurements per child, liver size and Doppler parameters of hepatic blood flow on liver elasticity values. The mean normal liver elasticity value in the study population was: 4.29±0.59 kilopascals (kPa). In neonates and infants, mean liver elasticity value was 4.63 (± 0.6) kPa, in preschoolers and elementary school children, 4.05 (± 0.57) kPa and 4.15 (± 0.52) kPa, respectively, and in adolescents, 4.39 (± 0.55) kPa. Values in neonates and infants as well as adolescents were significantly higher than in preschoolers and elementary school children (Kruskal-Wallis, P

The recent economic crisis has been linked with declines in population health. Evidence on the impact of the crisis on stillbirth rates is scarce. The aim of this study was to assess trends of stillbirth rates in Greece during the pre-crisis (2004-2008) and crisis period (2009-2015) and explore risk factors. Nationwide data (n = 1,276,816 births; 5023 stillbirths) were used to assess rates and trends through Poisson and joinpoint regressions. Multivariable Poisson regressions by nationality were fitted. The overall annual stillbirth rate was 3.9/1000 births with higher rates among non-Greeks (5.0/1000) than Greeks (3.7/1000). Non-significant decreasing trends were noted for Greeks (- 0.5%, 95% confidence interval [CI] - 1.4, 0.4%) versus non-significant increasing trends in non-Greeks (1.4%, 95% CI - 0.5, 3.3%). After adjusting for possible confounders, the relative stillbirth risk (RR) increased during the crisis versus the pre-crisis period (RR

ObjectiveTo study trends of infant mortality rate (IMR) and neonatal mortality rate in Greece during the period 2004–2016 and explore the role of sociodemographic factors in the years of crisis.DesignNationwide individual data for live births and infant (0–11 months) deaths provided by the Hellenic Statistical Authority were examined using Poisson, joinpoint regression and interrupted time series (ITS) analyses.SettingGreece.ParticipantsAll infant deaths (n=4862) over the 13-year period, of which 87.2% were born to Greek mothers, and respective live births.Main outcome measuresEvolution of IMR (0–364 days), early (ResultsBy Poisson regression, overall, during the study period, among infants of Greek mothers, IMR and PNMR declined significantly (−0.9%; 95% CI −1.7% to −0.1% and −1.6%; −3.0% to −0.2% annually, respectively), although differentially by place of residence (IMRurban: −2.1%; −2.9% to −1.3%, IMRrural: +10.6%; 7.6% to 13.6%). By contrast, among infants of non-Greek mothers, the low starting IMR/ENMR/LNMR/PNMR increased significantly (max ENMR:+12.5%; 8.6% to 16.5%) leading to a non-significant time–trend pattern overall in Greece. The inverse associations of HDI with IMR, ENMR and PNMR were restricted to Greek mothers’ infants. Joinpoint regression analyses among Greek mothers’ infants indicated non-significant increasing trends of IMR and ENMR following the crisis (+9.3%, 2012–2016, p=0.07 and +10.2%, 2011–2016, p=0.06, respectively). By contrast, the high (+17.1%; 8.1% to 26.9%, p=0.002) IMR increases among non-Greek infants were restricted to 2004–2011 and equalised to those of Greek mothers’ infants thereafter. ITS analyses in preset years (2008, 2010, 2012) identified significantly increasing trends in IMR, LNMR and PNMR after 2012, and in ENMR after 2010, among Greek mothers’ infants.ConclusionsHDI and rural residence were significantly associated with IMR. The strongly decreasing IMR trends among Greek-mothers’ infants were stagnated after a lag time of ~4 years of crisis approximating the previously sharply increasing trends among non-Greeks.

To determine if preterm birth is associated with components of the metabolic syndrome in adult life.A structured literature search was performed using PubMed. All comparative studies reported metabolic and cardiovascular outcomes in adults (≥18 years of age) born preterm (37 weeks of gestation) compared with adults born at term (37-42 weeks of gestation) and published through March 2018 were included. The major outcomes assessed were body mass index, waist circumference, waist-to-hip ratio, fat mass, systolic blood pressure (SBP), diastolic blood pressure (DBP), 24-hour SBP, 24-hour DBP, endothelium-dependent brachial artery flow-mediated dilation, carotid intima-media thickness, pulse wave velocity, fasting glucose and insulin, Homeostasis Model Assessment-Estimated Insulin Resistance Index, and lipid profiles. Quality appraisal was performed using a modified version of the Newcastle-Ottawa scale. A meta-analysis was performed for comparable studies which reported sufficient data.Forty-three studies were included, including a combined total of 18 295 preterm and 294 063 term-born adults. Prematurity was associated with significantly higher fat mass (P = .03), SBP (P .0001), DBP (P .0001), 24-hour SBP (P .001), and 24-hour DBP (P .001). Furthermore, preterm-born adults presented higher values of fasting glucose (P = .01), insulin (P = .002), Homeostasis Model Assessment-Estimated Insulin Resistance Index (P = .05), and total cholesterol levels (P = .05) in comparison with adults born at term, in random effect models. No statistically significant difference was found between preterm and term-born adults for the other outcomes studied.Preterm birth is strongly associated with a number of components of the metabolic syndrome and cardiovascular disease in adult life.

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.

Familial hypocalciuric hypercalcemia (FHH) is an autosomal dominant disorder, associated with inactivating mutations of the calcium-sensing receptor (CaSR). To evaluate the functional significance of a CaSR mutation, identified in a young infant who presented with hypercalcemia and hypocalciuria. The CaSR gene coding sequences were analyzed by polymerase chain reaction amplification and direct sequencing analysis. The mutation identified was introduced by site-directed mutagenesis into a wild-type (WT) CaSR plasmid, and human embryonic kidney 293 T cells were transfected with either the WT or mutant CaSR. The function of the mutated CaSR protein was analyzed by evaluating the free intracellular calcium [(Ca2+)i] response after challenge with extracellular calcium (Ca2+). We identified a heterozygous mutation c.772_773delGTinsA in exon 4 resulting in the substitution of amino acid valine (Val) with amino acid arginine (Arg) and the premature pause of the translation 46 amino acids later (Val258ArgfsTer47). Functional assay showed that cells transfected with the mutant CaSR had a significantly poorer response to extracellular Ca2+ stimulation compared with the WT. We have shown that the c.772_773delGTinsA mutation causes a significant alteration of CaSR function leading to features of FHH in an affected young infant since the first months of life.

Summary Background Healthcare-associated infections (HCAIs) are associated with increased morbidity and mortality and with excess costs. Central line-associated bloodstream infections (CLABSIs) are the most common HCAIs in neonates and children. Aim To establish national benchmark data for rates of CLABSI in neonatal and paediatric intensive care units (NICUs and PICUs) and paediatric oncology units (ONCs). Methods Active surveillance for CLABSI was conducted from June 2016 to February 2017. A collaborative of 14 NICUs, four PICUs, and six ONCs participated in the programme. Surveillance definitions of central line (CL), central line utilization (CLU) ratio, CLABSI event, and CLABSI rate were based on the Centers for Disease Control and Prevention's 2014 National Healthcare Safety Network criteria. Medical records were assessed daily for calculating CL-days, patient-days, and susceptibility of isolated organisms. Findings A total of 111 CLABSI episodes were recorded. The overall mean CLABSI rate was 4.41 infections per 1000 CL-days, and the CLU ratio was 0.31. CLABSI rates were 6.02 in NICUs, 6.09 in PICUs, and 2.78 per 1000 CL-days in ONCs. A total of 123 pathogens were isolated. The most common pathogens were Enterobacteriaceae (36%), followed by Gram-positive cocci (29%), non-fermenting Gram-negative bacteria (16%), and fungi (16%). Overall, 37% of Gram-negative pathogens were resistant to third-generation cephalosporins and 37% to carbapenems. Conclusion Nationally representative CLABSI rates were determined for paediatric patients. These data could be used to benchmark and serve as baseline data for the design and evaluation of infection control and antimicrobial stewardship interventions.

To critically assess the effectiveness of complementary/alternative medicine modalities, comprising body/mind stress-releasing techniques, on the breastfeeding (BF) success of mothers of full-term newborns.Literature review in Medline and other available database sources until December 2015, and critical analysis of pooled data. The study selection included randomized-controlled trials, case-control studies, and case series.The total number of analyzed studies was 9. Among them, three represented level-I, two level-II, one level-III, and three level-IV evidence. The pooled maternal population was 2135. Interventions that could influence cognition management seem effective in improving BF initiation and duration (strength of recommendation B), manual relaxation techniques in promoting BF initiation (strength of recommendation B), and auditory-mediated mind guidance in promoting BF duration (strength of recommendation C). The implementation of environmental sensory stimulations improves maternal perception about breastfeeding practice (strength of recommendation C).Certain methods of complementary and alternative medicine show positive effect on breastfeeding. Further studies with good quality evidence, dedicated follow-up of the families after discharge, and strict definitions of breastfeeding and weaning are necessary to confirm the effectiveness of the identified interventions.

The aims of this study were to investigate gross motor development in Greek infants and establish AIMS percentile curves and to examine possible association of AIMS scores with socioeconomic parameters.Mean AIMS scores of 1068 healthy Greek full-term infants were compared at monthly age level with the respective mean scores of the Canadian normative sample. In a subgroup of 345 study participants, parents provided, via interview, information about family socioeconomic status. Multiple linear regression analysis was performed to evaluate the relationship of infant motor development with socioeconomic parameters.Mean AIMS scores did not differ significantly between Greek and Canadian infants in any of the 19 monthly levels of age. In multiple linear regression analysis, the educational level of the mother and also whether the infant was being raised by grandparents/babysitter were significantly associated with gross motor development (p=0.02 and p0.001, respectively), whereas there was no significant correlation of mean AIMS scores with gender, birth order, maternal age, paternal educational level and family monthly income.Gross motor development of healthy Greek full-term infants, assessed by AIMS during the first 19months of age, follows a similar course to that of the original Canadian sample. Specific socioeconomic factors are associated with the infants' motor development.

The epidemic pattern of respiratory syncytial virus (RSV) infection during long periods and the factors that determine seasonality are not well studied. In order to correlate the RSV epidemic activity with climate parameters, we conducted a retrospective study of children (0-14 year) who were hospitalized because of respiratory tract infection and had an RSV test performed in the major tertiary pediatric hospital of Greece during a 12-year period (2002-2013). Daily data regarding temperature and humidity were obtained from the Hellenic National Meteorological Service. A total of 2030/7516 (27%) children were tested positive for RSV infection. Among RSV positive children 1945/2030 (95.8%) were infants1 year. A peak of RSV activity was measured in years 2002, 2003, and 2006 (35% positive). The RSV season in our area spanned from December to April, with higher incidence during January through March. The peak monthly RSV incidence was observed during February with mean temperature 10.34 °C and mean relative humidity 69.16%. Regarding climate conditions, a statistically significant positive correlation was found between monthly RSV activity and mean monthly relative humidity (rho = 0.66, P-value = 0.02), whereas a negative correlation was found with mean monthly temperature (rho = -0.81, P-value = 0.002). However, in the multivariable analysis, only the effect of mean monthly temperature remained statistically significant (IRR = 0.72, 95% CI: 0.68, 0.80). Further understanding of RSV seasonality in different geographic areas would be important in order to timely implement preventing strategies with immunoprophylaxis or future RSV vaccines.

Background Adipocyte fatty acid binding protein (a-FABP) has been suggested to play an important role in the pathogenesis of metabolic syndrome. Preterm infants are at risk for the later development of insulin resistance, and, possibly, other components of metabolic syndrome. Aim To determine circulating levels of a-FABP in preterm infants and examine possible associations of a-FABP with metabolic indices (serum lipids, glucose, and insulin levels, and homeostasis model assessment index of insulin resistance [HOMA-IR]), levels of leptin and adiponectin, anthropometric parameters and weight gain. Study design Prospective cohort study. Subjects 55 healthy preterm (mean [SD] gestational age 32.8 [1.8] weeks) and 23 fullterm infants (reference group). Outcome measures Serum a-FABP, lipids, glucose, insulin, leptin and adiponectin levels at 31.9 [10.4] days of life. Results Serum a-FABP levels did not differ significantly between preterm and fullterm infants. A-FABP levels correlated positively with total-cholesterol [ total-C ] in both preterm and fullterm infants ( β = 0.33; p = 0.01 and β = 0.33; p = 0.04, respectively). In addition to total-C, weight gain correlated independently with a-FABP levels in preterm infants ( β = 0.36, p = 0.01). Conclusions An association between a-FABP levels and indices of insulin resistance was not present in infants studied. As the development of insulin resistance in children born prematurely is possibly associated with weight gain in early postnatal life, follow-up of our study population is necessary to demonstrate whether a-FABP levels, shown to correlate with weight gain in preterm infants, are a predictive marker for the later development of insulin resistance in these infants.

ObjectiveThe phenotype associated with heterozygous HNF4A gene mutations has recently been extended to include diazoxide responsive neonatal hypoglycemia in addition to maturity-onset diabetes of the young (MODY). To date, mutation screening has been limited to patients with a family history consistent with MODY. In this study, we investigated the prevalence of HNF4A mutations in a large cohort of patients with diazoxide responsive hyperinsulinemic hypoglycemia (HH).Subjects and methodsWe sequenced the ABCC8, KCNJ11, GCK, GLUD1, and/or HNF4A genes in 220 patients with HH responsive to diazoxide. The order of genetic testing was dependent upon the clinical phenotype.ResultsA genetic diagnosis was possible for 59/220 (27%) patients. KATP channel mutations were most common (15%) followed by GLUD1 mutations causing hyperinsulinism with hyperammonemia (5.9%), and HNF4A mutations (5%). Seven of the 11 probands with a heterozygous HNF4A mutation did not have a parent affected with diabetes, and four de novo mutations were confirmed. These patients were diagnosed with HI within the first week of life (median age 1 day), and they had increased birth weight (median +2.4 SDS). The duration of diazoxide treatment ranged from 3 months to ongoing at 8 years.ConclusionsIn this large series, HNF4A mutations are the third most common cause of diazoxide responsive HH. We recommend that HNF4A sequencing is considered in all patients with diazoxide responsive HH diagnosed in the first week of life irrespective of a family history of diabetes, once KATP channel mutations have been excluded.

Adiponectin has potent insulin-sensitizing effects, improves lipid metabolism, and potentially protects against the development of metabolic syndrome. Thus, increasing adiponectin levels in preterm infants at risk for developing metabolic syndrome may be of special interest. The aim of this study was to examine the effects of dietary long-chain polyunsaturated fatty acids (LCPUFA) on serum adiponectin and lipid concentrations in preterm infants. Adiponectin and lipid levels of 60 healthy preterm infants [gestational age 32.7 (1.9) wk] randomly assigned to be fed either 1) a formula containing LCPUFA [arachidonic and docosahexanoic] (+LCPUFA group) or 2) the same formula without LCPUFA (-LCPUFA/control group), were determined at mean (SD) 33.8 (11.7) d. Adiponectin and HDL-C concentrations were significantly higher in the +LCPUFA group than in controls (p = 0.002 and p = 0.01, respectively); whereas, triglyceride levels were lower (p = 0.06). Adiponectin correlated positively with HDL-C levels and negatively with triglyceride levels in the +LCPUFA group but not in the controls. In conclusion, circulating adiponectin concentrations were higher in preterm infants fed a formula containing LCPUFA than infants fed an LCPUFA-free formula and they correlated with lipidemic profile.

Objective: To determine the circulating concentrations of adiponectin in preterm infants and examine the possible associations with anthropometric parameters, weight gain, leptin and insulin levels. Design: Prospective study. Setting: University Hospital Neonatal Care Unit. Study population: 62 preterm [mean(SD) gestational age 32.0(2.1) weeks] and 15 fullterm infants, as reference group. Interventions: Blood sampling at discharge [40.9 (14.8) days of life] in preterm infants and at a comparable postnatal age in fullterm infants. All infants were fed with the same commercial formula, but in 9 preterm infants the formula contained long-chain polyunsaturated fatty acids (LCPUFAs; arachidonic and docosahexaenoic). Main outcome measures: Serum adiponectin, leptin and insulin levels in the entire study population. Associations of adiponectin levels were tested only in the preterm group. Results: Serum adiponectin concentrations were lower in preterm [40.8(15.3) μg/ml] than fullterm infants [53.1(16.0) μg/ml, p

Introduction Rotavirus (RV) infection in neonatal age can be mild or even asymptomatic. Several studies have reported that RV is responsible for 31%-87% of pediatric nosocomial diarrhea and causes gastroenteritis outbreaks in pediatric and neonatal units. Objectives Study clinical characteristics, genotypes and risk factors of RV infection in neonatal age. Methods A prospective study was conducted from April 2009 till April 2013 in the neonatal special care unit of the largest tertiary pediatric hospital of Greece. Fecal samples and epidemiological data were collected from each neonate with gastrointestinal symptoms. RV antigen was detected with a rapid immunochromatography test. RV positive samples were further genotyped with RT PCR and sequencing using specific VP7 and VP4 primers. Results Positive for RV were 126/415 samples (30.4%). Mean age of onset was 18 days. Seventy four cases (58%) were hospital acquired. Seasonality of RV infection did not differ significantly throughout the year with the exception of 4 outbreaks. Genotypes found during the study period were G4P[8] (58.7%), G1P[8] (14.7%), G12P[8] (9.3%), G3P[8] (9.3%), G12P[6] (5.3%), G9P[8] (1.3%) and G2P[4] (1.3%). RV cases presented with: diarrhea (81%), vomiting (26.2%), fever (34.9%), dehydration (28.6%), feeding intolerance (39.7%), weight loss (54%), whilst 19% of cases were asymptomatic. Comparing community with hospital acquired cases differences in clinical manifestations were found. Conclusions Significant incidence of nosocomially transmitted RV infection in neonatal age including asymptomatic illness exists. Genotypes causing nosocomial outbreaks are not different from community strains. Circulating vaccines can be effective in prevention of nosocomial RV infection through herd immunity.

Early diagnosis and treatment of neonatal infection is important to prevent morbidity and mortality. The gastrointestinal tract-derived hormones ghrelin and peptide YY (PYY), which participate in the regulation of food intake and energy balance, may also play roles in the inflammatory response. Their involvement in neonatal infection is not known.Plasma ghrelin and PYY(3-36) levels were serially measured (by ELISA) on Days 0, 1, 2, 3 and 7 following admission in 36-term neonates with febrile infection (22 of them were septic) and once in 20 healthy term neonates of similar postnatal age and gender distribution, as controls. Associations of ghrelin and PYY(3-36) levels with clinical and laboratory parameters, including anthropometrics, fever, leukocyte and platelet counts, serum glucose, C-reactive protein (CRP) and serum amyloid A levels, were assessed.Plasma ghrelin levels were significantly higher in infected neonates than in controls at each study day (p=0.009), whereas PYY(3-36) levels did not differ significantly between patients and controls at any day. In infected neonates, ghrelin levels on admission correlated negatively with serum glucose levels (p=0.003), whereas fever change during the course of infection was significantly associated with change of ghrelin levels (p=0.01). Receiver operating characteristic analysis of ghrelin levels resulted in significant areas under the curve (AUC) for detecting infected neonates on admission (AUC=0.728, p=0.005).Circulating ghrelin, but not PYY(3-36), levels are increased in neonates with infection, possibly reflecting and/or participating in the inflammatory process.

Background Only a few studies have been conducted with the objective of creating norms of the Alberta Infant Motor Scale (AIMS) for the assessment of gross motor development of preterm infants. The AIMS performance of preterm infants has been compared with that of the Canadian norms of full-term infants, but not with that of full-term infants of the same nationality. Moreover, the possible impact of prematurity-related morbidity factors on AIMS performance is unknown. Objectives The aims of this study were: (1) to evaluate AIMS trajectory in a large population of Greek preterm infants and create norms, (2) to compare it with the AIMS trajectory of Greek full-term infants, and (3) to examine the possible influence of neonatal morbidity on AIMS scores in the preterm sample. Design This was a cross-sectional study. Methods Mean AIMS scores were compared, per month (1–19), between 403 preterm infants (≤32 weeks of age, corrected for prematurity) and 1,038 full-term infants. In preterm infants, the association of AIMS scores with respiratory distress syndrome (RDS), intraventricular hemorrhage (IVH) of grade ≤III, bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), and sepsis was assessed by hierarchical regression analysis. Results Alberta Infant Motor Scale scores were significantly lower in preterm infants than in full-term infants. Mean AIMS scores in preterm infants were significantly associated with RDS (b=−1.93; 95% CI=−2.70, −1.16), IVH (b=−0.97; 95% CI=−1.69, −0.25), and ROP (b=−1.12; 95% CI=−1.99, −0.24) but not with BPD or sepsis in hierarchical regression analysis. Conclusions Alberta Infant Motor Scale norms were created for Greek preterm infants. This study confirms that AIMS trajectories of preterm infants are below those of full-term infants of the same nationality. The influence of morbidity factors, including RDS, IVH, and ROP, should be taken into account when administering the AIMS in preterm infants.

Obesity and cardiovascular disease (CVD) often co-exist, but the pathophysiologic mechanisms that link the two are not fully understood. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is involved in the modification of lipids within atheromatous plaques. Recently, circulating Lp-PLA2 was found to be predictive of thromboembolic episodes in adults, independently of a variety of other potential risk factors, including markers of inflammation, renal function, and hemodynamic stress. However, the function of this lipase and its importance as a biomarker in childhood obesity is much less studied. The aim of the study was to study Lp-PLA2, a non-traditional risk factor of CVD, in obese children.Sixty-seven lean [39 boys and 28 girls, mean body mass index (BMI) z-score -0.2±0.8] and 66 obese (32 boys and 34 girls, mean BMI z-score 4.4±1.2) age-matched (p=0.251) children, aged 6-12 years, were studied. BMI z-score was calculated based on the Greek BMI growth curves, and children were categorized as obese according to the Cole criteria. All children underwent physical examination and a fasting morning blood sample was obtained for glucose, insulin, lipid profile, and Lp-PLA2 assessment. Plasma concentrations of Lp-PLA2 were determined by a commercially available Lp-PLA2 enzyme-linked immunosorbent assay kit (PLAC Test), while other measurements were performed using standard methods.Plasma Lp-PLA2 levels were significantly higher in obese children (322.5±77.8 ng/mL) compared with normal-weight ones (278.0±64.4 ng/mL, p0.001). Lp-PLA2 concentrations were significantly correlated with the BMI z-score (p=0.004). Receiver operating characteristic analysis on Lp-PLA2 values resulted in significant areas under the curve (AUC) for distinguishing between obese and normal-weight groups of children (AUC, 0.726; p0.001).We found significantly higher Lp-PLA2 levels in obese children than lean controls. Interestingly, they all had levels200 ng/mL, which are considered to correlate with atherosclerosis and a high thromboembolic risk in adults. The positive correlation of Lp-PLA2 with BMI suggests that Lp-PLA2 might be the link between obesity and increased cardiovascular risk, which can be elevated even at a very young age. Measurement of Lp-PLA2 in plasma could therefore represent a further biomarker for assessing increased CVD risk in obese children and adolescents.

Abnormal glucose tolerance is a frequent late complication of cystic fibrosis (CF), but the prevalence of CF-related diabetes mellitus (CFRD) in children less than 10 y old is less than 2%. The youngest child with CFRD reported to date was 6 mo of age. Insulinopenia is the primary cause of abnormal glucose tolerance/CFRD, but it is unknown whether it may begin in the neonatal period. We describe a case of a neonate with CF who presented with hyperglycaemia in the diabetic range and marked insulinopenia. Insulinopenia and impaired glucose tolerance were permanent findings at 6 and 15 mo of age.This case suggests that abnormal glucose tolerance/diabetes may occur much earlier in the course of CF, even during neonatal age. Careful follow-up and further studies in CF infants could reveal that the real incidence of glucose intolerance and diabetes in this age group has been underestimated.

Background: Peptide YY (PYY) and ghrelin are gastrointestinal tract–derived hormones that play roles in the regulation of food intake and energy balance. Negative energy balance often occurs in hospitalized preterm infants. Methods: To measure serum concentrations of PYY in preterm and full-term infants and to investigate their correlations with anthropometric characteristics, food intake, and serum ghrelin concentrations, we measured serum PYY and ghrelin concentrations by RIA in 62 healthy preterm infants [mean (SD) gestational age, 32.0 (2.1) weeks; postnatal age, 40.9 (14.8) days] and 15 healthy full-term infants of comparable postnatal age. All of the infants were formula-fed every 3 h. Results: PYY concentrations were significantly higher in preterm [1126.2 (215.4) ng/L] than in full-term infants [825.3 (234.4) ng/L; P Conclusions: Circulating concentrations of PYY may increase in preterm infants to compensate for the negative body-weight balance. The physiologic mechanisms behind the correlation between PYY and ghrelin remain to be elucidated.

Background. suPAR, the soluble form of the urokinase-type plasminogen activator receptor, has been identified as a biomarker of infection in adults but its properties in neonatal infection are not known.Methods. Plasma suPAR levels were determined by ELISA in 47 term neonates with infection (19 bacterial and 28 viral) and in 18 healthy neonates as controls. Thirteen out of 47 infected neonates were septic. In all infected neonates, suPAR levels were repeated at 24 hours, 48 hours, 3–5 days, and 7–10 days following admission.Results. Plasma suPAR levels were significantly increased in infected neonates upon admission, whereas they were highest in septic neonates, in comparison with controlsP<0.001and correlated positively with serum CRP levels (P=0.001). At infection subsidence, suPAR concentrations decreased significantly in comparison with baseline (P<0.001) but remained higher than in controls (P=0.01). Receiver operating characteristic analysis resulted in significant areas under the curve for detecting either infected or septic neonates, but not for discriminating between bacterial and viral cause of infection.Conclusions. suPAR is a diagnostic biomarker of infection or sepsis in term neonates; however, it cannot discriminate bacterial from viral infections and also its utility for monitoring the response to treatment is questioned.

Two infants with recurrence of herpes simplex virus (HSV) encephalitis are reported. Both patients developed HSV encephalitis during their neonatal period and were treated with iv acyclovir. Long-term oral acyclovir prophylaxis was given thereafter. At the age of 8 and 11 months respectively, both babies, while under oral acyclovir prophylaxis, presented a second episode of HSV encephalitis. An inadequate dose of suppressive oral acyclovir therapy may be responsible for the recurrence of encephalitis in these two babies. Conclusion: the present observations emphasise the need for very long follow-up of any infant who has suffered from neonatal herpes simplex virus encephalitis and the need for careful prospective controlled studies in order to define the appropriate treatment regimen (initial plus prophylaxis) for neonates with herpes simplex virus infections.

Phenotypic variation in CHARGE syndrome remains unexplained. A subcategory of CHARGE patients show overlapping phenotypic characteristics with DiGeorge syndrome (thymic hypo/aplasia, hypocalcemia, T-cell immunodeficiency). Very few have been tested or reported to carry a mutation of the CHD7 (chromodomain helicase DNA-binding domain) gene detected in two-thirds of CHARGE patients. In an attempt to explore the genetic background of a severe CHARGE/DiGeorge phenotype, we performed comparative genomic array hybridization in an infant carrier of a CHD7 mutation. The high-resolution comparative genomic array hybridization revealed interesting findings, including a deletion distal to the DiGeorge region and disruptions in other chromosomal regions of genes implicated in immunological and other functions possibly contributing to the patient's severe phenotype and early death.

Background. Influenza is associated with an increased risk for serious illness, hospitalization, and mortality in infants aged

Microvillus inclusion disease (MVID), a rare severe congenital enteropathy characterized by intracytoplasmic microvillous inclusions and variable brush border atrophy on intestinal epithelial cells histology, is associated with defective synthesis or abnormal function of the motor protein myosin Vb encoded by the MYO5B gene. Although MYO5B gene is expressed in all epithelial tissues, it is unclear so far whether organs other than intestine are affected in MVID patients. We report a case of an infant with MVID who presented liver dysfunction, hematuria, and Pneumocystis jiroveci pneumonia during the course of the disease. It is discussed whether extraintestinal manifestations in this patient are secondary consequences of MVID or might be features of the disease associated with altered MYO5B function. Conclusions: MVID is classically included in the differential diagnosis of congenital diarrhea of secretory type. Recent advances in our knowledge regarding the role of myosin Vb in the pathophysiology of MVID is expected to clarify the clinical spectrum of the disease and the possible primary involvement of organs other than intestine.

Neonatal immune neutropenia (NIN) is a rare, but potentially life-threatening, disorder caused by maternal alloantibodies recognizing paternal neutrophil antigens on fetal cells. Alloantibodies directed against the human neutrophil alloantigen system (HNA)-1 located on Fcγ receptor IIIb (FcγRIIIb) are most frequently implicated in NIN. In this report, we describe two cases of NIN with alloantibodies against FcγRIIIb, which did not match one of the known HNA-1a, -1b, or -1c specificities, but define a new antigen, HNA-1d.Neutrophil-reactive antibodies were detected by agglutination, microscopic immunofluorescence, and monoclonal antibody (MoAb)-specific immobilization of neutrophil antigens (MAIGA) assay. For epitope mapping of FcγRIIIb-reactive antibodies, recombinant chimeric variants of FcγRIIIb were used in the MAIGA assay. Genotyping of FCGR3B was performed by allele-specific polymerase chain reaction.Both mothers were typed FCGR3B*01+, *02-, *03+. Antibody screening revealed the presence of alloantibodies reactive with FcγRIIIb encoded by FCGR3B*02, but not with FcγRIIIb encoded by FCGR3B*03. MAIGA with recombinant, partly chimeric FcγRIIIb variants demonstrated that the antigen recognized by maternal antibodies is characterized by two amino acids, Ala78 and Asp82. Among the FCGR3B alleles, the sequence Ala78---Asn82 is exclusively encoded by FCGR3B *02.A previously unrecognized second antigen, HNA-1d, is present on FcγRIIIb encoded by FCGR3B*02. This antigen is characterized by the sequence Ala78---Asn82. It appears that only individuals carrying the HNA-1c phenotype can form anti-HNA-1d alloantibodies. The HNA-1 system now consists of four antigens encoded by three alleles.

Objectiveα-Klotho (α-KL), a protein with antiaging properties, regulates phosphate, calcium, and bone metabolism, induces resistance to oxidative stress, and may participate in insulin signaling. The role of α-KL in neonates, known to be prone to metabolic disturbances and oxidative stress, is not known. The aim of this study was to evaluate circulating soluble α-KL concentrations in preterm and full-term neonates and unravel possible correlations with growth, metabolism, and indices of oxidative stress.DesignProspective study.MethodsPlasma-soluble α-KL levels were determined by specific ELISA in 50 healthy neonates (25 preterm, mean (s.d.) gestational age (GA) 33.7 (1.1) weeks, and 25 full-term infants) at days 14 and 28 of life. Associations of α-KL with anthropometric, metabolic parameters, and indices of oxidative stress were examined.Resultsα-KL levels were significantly higher in full-term than in preterm infants at both days 14 (1099 (480) pg/ml vs 884 (239) pg/ml respectively; PPPβ=0.32, P=0.001), body weight (β=0.34, P=0.001), body length (β=0.33, P=0.001), 1,25-dihydroxy-vitamin D level (β=0.24, Pβ=0.20, PConclusionsSoluble α-KL levels rise as GA and postnatal age advance in neonates and may have an impact on vitamin D metabolism and oxidative stress. Whether α-KL may have a role in the regulation of infants' growth should be further studied.

Young infants are at increased risk for influenza-associated serious illness, onset of complications, utilization of health-care services, and hospitalization. We investigated the feasibility and acceptance of an influenza vaccination (cocooning) strategy by household contacts implemented in a maternity hospital and the neonatal unit of a pediatric hospital in Athens. A total of 224 mothers (mean age: 30.2 years) who gave birth to 242 neonates were studied. Of them, 165 (73.7%) mothers were vaccinated. Multiple logistic regression revealed that statistically significant factors associated with increased vaccination rates among mothers were: being of Roma origin (p-value = 0.002), being an immigrant (p-value = 0.025), giving birth to a neonate with birth weight

Oseltamivir was administered at 1.0 mg/kg b.i.d. to 13 neonates exposed to influenza H1N1. No influenza, neurologic, or laboratory adverse effects occurred. The mean C max values for oseltamivir and oseltamivir car-boxylate were found to be lower than those reported for children 1 to 5 years old, whereas T max values were similar to children 1 to 5 years old. Age and gender were found to significantly affect oseltamivir clearance. Key Words: neonates, influenza H1N1, oseltamivir; prophylaxis, pharmacokineticsAccepted for publication December 17, 2011.From the *Department for Interventions in Health-Care Facilities, Hellenic Centre for Diseases Control and Prevention, Athens, Greece; †Department of Pharmaceutical Technology, School of Pharmacy, University of Athens, Athens, Greece; ‡Neonatal Unit, First Department of Pediatrics, University of Athens, Aghia Sophia Children’s Hospital, Athens, Greece; §Laboratory of Biopharmaceutics Pharmacokinetics, School of Pharmacy, University of Athens, Athens, Greece; ¶Department of Pharmaceutical Chemistry, School of Pharmacy, University of Athens, Athens, Greece; ||Laboratory of Prenatal and Neonatal Screening, Neoscreen Ltd, Athens, Greece; and **First Depart-ment of Pediatrics, University of Athens, Aghia Sophia Children’s Hospital, Athens, Greece.The authors have no funding or conflicts of interest to disclose.Address for correspondence: Helena C. Maltezou, MD, PhD, Department for Interventions in Health-Care Facilities, Hellenic Center for Diseases Control and Prevention, 3-5 Agrafon St, Athens 15123 Greece; E-mail: helen-maltezou@ath.forthnet.gr.Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www.pidj.com).Copyright © 2012 by Lippincott Williams & WilkinsDOI: 10.1097/INF.0b013e3182472f28

Pasteurella multocida is usually transmitted by animal contact; however, in a significant proportion of cases, no animal exposure can be identified. Although vertical transmission has been identified in neonates, horizontal human-to-human spread has not been documented. A case of neonatal sepsis and meningitis resulting from horizontal transmission of P. multocida is described.