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    tom stiris

    The permanently growing mouse incisors exhibit all stages of tooth development along their inciso-apical axis at any time. Any disturbance or injury of the ameloblasts during enamel formation or maturation may result in permanent defects... more
    The permanently growing mouse incisors exhibit all stages of tooth development along their inciso-apical axis at any time. Any disturbance or injury of the ameloblasts during enamel formation or maturation may result in permanent defects in the finished enamel since the enamel does not undergo repair or remodeling after formation. In order to increase our understanding of how hypoxia affects enamel formation, we induced severe acute hypoxia in adult mice and observed its effects on the enamel in incisors. Incisors from hypoxic mice were obtained 5 and 49 days after the hypoxic insult. Hypoxic and control incisors were dissected out and observed by scanning electron microscopy (SEM). Incisors were subsequently ground longitudinally or transversely, etched, and observed again by SEM. The nature and position of defects were considered in relation to the configuration and dynamics of the incisors. The effect of hypoxia varied considerably, among mice, among incisors, and among ameloblasts. Affected enamel showed hypoplasia with hypomineralization or hypomineralization without hypoplasia. Vascular endothelial growth factor (VEGF) showed considerably stronger labeling in hypoxic compared to control ameloblasts. The present study demonstrates quantitative and qualitative defects in the enamel reflecting the vulnerability of ameloblasts toward severe acute hypoxia in mouse incisors.
    Introduction: Predicting impairment in preterm children is challenging. Our aim is to explore the association between MRI at term-equivalent age (TEA) and neurocognitive outcomes in late childhood and to assess whether the addition of EEG... more
    Introduction: Predicting impairment in preterm children is challenging. Our aim is to explore the association between MRI at term-equivalent age (TEA) and neurocognitive outcomes in late childhood and to assess whether the addition of EEG improves prognostication. Methods: This prospective observational study included forty infants with gestational age 24 + 0–30 + 6. Children were monitored with multichannel EEG for 72 h after birth. Total absolute band power for the delta band on day 2 was calculated. Brain MRI was performed at TEA and scored according to the Kidokoro scoring system. At 10–12 years of age, we evaluated neurocognitive outcomes with Wechsler Intelligence Scale for Children 4th edition, Vineland adaptive behavior scales 2nd edition and Behavior Rating Inventory of Executive Function. We performed linear regression analysis to examine the association between outcomes and MRI and EEG, respectively, and multiple regression analysis to explore the combination of MRI and E...
    Objective. To overcome the effects of site differences in EEG-based brain age prediction in preterm infants. Approach. We used a ‘bag of features’ with a combination function estimated using support vector regression (SVR) and feature... more
    Objective. To overcome the effects of site differences in EEG-based brain age prediction in preterm infants. Approach. We used a ‘bag of features’ with a combination function estimated using support vector regression (SVR) and feature selection (filter then wrapper) to predict post-menstrual age (PMA). The SVR was trained on a dataset containing 138 EEG recordings from 37 preterm infants (site 1). A separate set of 36 EEG recordings from 36 preterm infants was used to validate the age predictor (site 2). The feature distributions were compared between sites and a restricted feature set was constructed using only features that were not significantly different between sites. The mean absolute error between predicted age and PMA was used to define the accuracy of prediction and successful validation was defined as no significant differences in error between site 1 (cross-validation) and site 2. Main results. The age predictor based on all features and trained on site 1 was not validate...
    Vitamin A has a key role in lung development and its deficiency is associated with an increased risk of bronchopulmonary dysplasia. This secondary cohort analysis of the ImNuT trial (Immature, Nutrition Therapy NCT03555019) aimed to (1)... more
    Vitamin A has a key role in lung development and its deficiency is associated with an increased risk of bronchopulmonary dysplasia. This secondary cohort analysis of the ImNuT trial (Immature, Nutrition Therapy NCT03555019) aimed to (1) explore vitamin A status in preterm infants <29 weeks gestation and (2) assess the influence of inflammation and postnatal dexamethasone exposure on vitamin A concentrations in blood. We report detailed information on vitamin A biochemistry, vitamin A intake, markers of inflammation and dexamethasone exposure. After four weeks of age, infants exposed to dexamethasone (n = 39) showed higher vitamin A concentrations compared to unexposed infants (n = 41); median (IQR) retinol was 1.0 (0.74, 1.5) vs. 0.56 (0.41, 0.74) µmol/L, p < 0.001. Pretreatment retinol concentrations were lower in the dexamethasone group compared to non-exposed infants (p < 0.001); 88% vs. 60% of the infants were considered deficient in vitamin A (retinol < 0.7 µmol/L) ...
    PurposeHuman milk (HM) composition is influenced by factors, like maternal diet and body stores, among other factors. For evaluating the influence of maternal fatty acid (FA) status on milk FA composition, the correlation between FA... more
    PurposeHuman milk (HM) composition is influenced by factors, like maternal diet and body stores, among other factors. For evaluating the influence of maternal fatty acid (FA) status on milk FA composition, the correlation between FA content in HM and in maternal plasma, erythrocytes, and adipose tissue was investigated.Methods223 European women who delivered at term, provided HM samples over first four months of lactation. Venous blood and adipose tissue (only from mothers who consented and underwent a C-section delivery) were sampled at delivery. FAs were assessed in plasma, erythrocytes, adipose tissue, and HM. Evolution of HM FAs over lactation and correlations between FA content in milk and tissues and between mother’s blood and cord blood were established.ResultsDuring lactation, arachidonic acid (ARA) and docosahexaenoic acid (DHA) significantly decreased, while linoleic acid (LA), alpha-linolenic acid (ALA), and eicosapentaenoic acid (EPA) remained stable. Positive correlatio...
    Background Evidence regarding the predictive value of early amplitude-integrated electroencephalography (aEEG)/EEG on neurodevelopmental outcomes at school age and beyond is lacking. We  aimed to investigate whether there is an... more
    Background Evidence regarding the predictive value of early amplitude-integrated electroencephalography (aEEG)/EEG on neurodevelopmental outcomes at school age and beyond is lacking. We  aimed to investigate whether there is an association between early postnatal EEG and neurocognitive outcomes in late childhood. Methods This study is an observational prospective cohort study of premature infants with a gestational age <28 weeks. The total absolute band powers (tABP) of the delta, theta, alpha, and beta bands were analyzed from EEG recordings during the first three days of life. At 10–12 years of age, neurocognitive outcomes were assessed using the Wechsler Intelligence Scale for Children 4th edition (WISC-IV), Vineland adaptive behavior scales 2nd edition, and Behavior Rating Inventory of Executive Function (BRIEF). The mean differences in tABP were assessed for individuals with normal versus unfavorable neurocognitive scores. Results Twenty-two infants were included. tABP value...
    Inhaled nitric oxide therapy in neonates and children: reaching a European consensus
    Background The relationship between human milk oligosaccharides (HMOs) and infant growth and adiposity is not fully understood and comprehensive studies are missing from the current literature. Methods We screened and recruited 370... more
    Background The relationship between human milk oligosaccharides (HMOs) and infant growth and adiposity is not fully understood and comprehensive studies are missing from the current literature. Methods We screened and recruited 370 healthy, pregnant women and their infants from seven European countries. Breastmilk samples were collected using standardized procedures at six time points over 4 months, as were infant parameters. Correlations and associations between HMO area under the curve, anthropometric data, and fat mass at 4 months were tested. Results Lacto-N-neotetraose had a negative correlation with the change in length ( r s = −0.18, P  = 0.02). Sialyllacto-N-tetraose c (LSTc) had a positive correlation with weight for length ( r s = 0.19, P  = 0.015). Infants at the 25th upper percentile were fed milk higher in 3′-sialyllactose and LSTc ( P  = 0.017 and P  = 0.006, respectively) compared to the lower 25th percentile of the weight-for-length z -score gain over 4 months of lactation. No significant associations between growth and body composition and Lewis or secretor-dependent HMOs like 2′-fucosyllactose were identified. Conclusions Changes in the HMO composition of breastmilk during the first 4 months appear to have little influence on infant growth and body composition in this cohort of healthy mothers and infants. Impact Modest associations exist between individual HMO and infant growth outcomes at least in healthy growing populations. Our study provides a comprehensive investigation of associations between all major HMO and infant growth and adiposity including several time points. Certain groups of HMOs, like the sialylated, may be associated with adiposity during the first months of lactation. HMO may modulate the risk of future metabolic disease. Future population studies need to address the role of specific groups of HMOs in the context of health and disease to understand the long-term impact.
    Background Current nutritional management of infants born very preterm results in significant deficiency of the essential fatty acids (FAs) arachidonic acid (ARA) and docosahexaenoic acid (DHA). The impact of this deficit on brain... more
    Background Current nutritional management of infants born very preterm results in significant deficiency of the essential fatty acids (FAs) arachidonic acid (ARA) and docosahexaenoic acid (DHA). The impact of this deficit on brain maturation and inflammation mediated neonatal morbidities are unknown. The aim of this study is to determine whether early supply of ARA and DHA improves brain maturation and neonatal outcomes in infants born before 29 weeks of gestation. Methods Infants born at Oslo University Hospital are eligible to participate in this double-blind randomized controlled trial. Study participants are randomized to receive an enteral FA supplement of either 0.4 ml/kg MCT-oil™ (medium chain triglycerides) or 0.4 ml/kg Formulaid™ (100 mg/kg of ARA and 50 mg/kg of DHA). The FA supplement is given from the second day of life to 36 weeks’ postmenstrual age (PMA). The primary outcome is brain maturation assessed by Magnetic Resonance Imaging (MRI) at term equivalent age. Second...
    Background: Subclinical mastitis (SCM) is an inflammatory condition of the mammary gland. We examined the effects of SCM on human milk (HM) composition, infant growth, and HM intake in a mother–infant cohort from seven European countries.... more
    Background: Subclinical mastitis (SCM) is an inflammatory condition of the mammary gland. We examined the effects of SCM on human milk (HM) composition, infant growth, and HM intake in a mother–infant cohort from seven European countries. Methods: HM samples were obtained from 305 mothers at 2, 17, 30, 60, 90, and 120 days postpartum. SCM status was assessed using HM Sodium (Na): Potassium (K) ratio >0.6. Levels of different macro- and micronutrients were analyzed in HM. Results: SCM prevalence in the first month of lactation was 35.4%. Mean gestational age at delivery was lower and birth by C-section higher in SCM mothers (p ≤ 0.001). HM concentrations of lactose, DHA, linolenic acid, calcium, and phosphorous (p < 0.05 for all) was lower, while total protein, alpha-lactalbumin, lactoferrin, albumin, arachidonic acid to DHA ratio, n-6 to n-3 ratio and minerals (iron, selenium, manganese, zinc, and copper) were higher (p < 0.001 for all) in mothers with SCM. There were no di...
    Human milk oligosaccharide (HMO) composition varies among lactating mothers and changes during the course of lactation period. Interindividual variation is largely driven by fucosyltransferase (FUT2 and FUT3) polymorphisms resulting in 4... more
    Human milk oligosaccharide (HMO) composition varies among lactating mothers and changes during the course of lactation period. Interindividual variation is largely driven by fucosyltransferase (FUT2 and FUT3) polymorphisms resulting in 4 distinct milk groups. Little is known regarding whether maternal physiological status contributes to HMO variability. We characterized the trajectories of 20 major HMOs and explored whether maternal pre-pregnancy body mass index (ppBMI), mode of delivery, or parity may affect milk HMO composition. Using longitudinal breastmilk samples from healthy mothers (n = 290) across 7 European countries, we characterized HMO composion and employed mixed linear models to explore associations of maternal characteristics with individual HMOs. We observed HMO-specific temporal trajectories and milk group dependencies. We observed relatively small but significant differences in HMO concentrations based on maternal ppBMI, mode of delivery and parity. Our findings su...
    Child trafficking is among the most lucrative criminal activities in the world and growing rapidly. Poverty, natural disasters, armed conflicts and, in particular, migration put vulnerable children at high risk of trafficking. Accurate... more
    Child trafficking is among the most lucrative criminal activities in the world and growing rapidly. Poverty, natural disasters, armed conflicts and, in particular, migration put vulnerable children at high risk of trafficking. Accurate statistics on child trafficking are not available due to its illegal nature. Moreover, trafficking may not be consistently recorded and reported by European countries, mainly because of different perceptions as to who is considered a victim of trafficking. Around 4000-5000 children were identified as presumed victims of trafficking in European Union countries from 2013 to 2014; this is an underestimate of the problem because many victims go unrecognised. Trafficking is linked with issues, such as forced marriage, begging, labour or domestic servitude, slavery and prostitution as well as sexual abuse and child pornography. It may also involve the use of children as soldiers or for criminal activities, such as theft and drug smuggling. Child trafficking...
    On the occasion of the 50th anniversary of the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN), its close partner associations submitted comments and felicitations which are presented here. These... more
    On the occasion of the 50th anniversary of the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN), its close partner associations submitted comments and felicitations which are presented here. These include words from the Latin American (LASPGHAN), North American (NASPGHAN) and Panarabian Societies (PASPGHAN) and the Commonwealth Association (CAPGHAN) of Paediatric Gastroenterology, Hepatology and Nutrition, the Federation of International Societies of Paediatric Gastroenterology, Hepatology and Nutrition (FISPGHAN), the European Academy of Pediatrics (EAP), the European Pediatric Association/Union of National Pediatric Societies (EPA-UNEPSA), the International Pediatric Association (IPA), the European Crohn's and Colitis Organisation (ECCO), European Society for Clinical Nutrition and Metabolism (ESPEN) , the Federation of European Nutrition Societies (FENS), and United European Gastroenterology (UEG).
    The European Academy of Paediatrics (EAP) is the paediatric section of the European Union of Medical Specialists (UEMS). The UEMS is responsible for the supervision and approval of training programmes in paediatrics and in its... more
    The European Academy of Paediatrics (EAP) is the paediatric section of the European Union of Medical Specialists (UEMS). The UEMS is responsible for the supervision and approval of training programmes in paediatrics and in its subspecialties. This implies also that EAP has the responsibility to address the training of all professionals working with children, to ensure that their paediatric competences and skills are adequate when dealing with children. The EAP has developed syllabi for paediatricians that provide standards of practice, and criteria for the assessment of competencies in trainees and training centres across Europe. The EAP recommends that all health care professionals working with children should have an officially approved training in child health in addition to formal qualifications in their own field. Moreover, the existing paediatric workforce must maintain their knowledge and skills with relevant continuous professional development and medical education in child ...
    Antimicrobial stewardship (AMS) aims to optimise treatment, minimise the risk of adverse effects and reduce health care costs. In addition, it is recognised as a key component to stop the current spread of antimicrobial resistance in... more
    Antimicrobial stewardship (AMS) aims to optimise treatment, minimise the risk of adverse effects and reduce health care costs. In addition, it is recognised as a key component to stop the current spread of antimicrobial resistance in Europe. Educational programmes are particularly important for the successful implementation of AMS. Training should start during medical school, continue during clinical training and be reinforced throughout postgraduate training. National core curricula for paediatric training should include passive and active training of competencies needed for AMS and future paediatricians should be skilled in taking leadership roles in AMS initiatives. Other core members of the paediatric AMS team should also receive training focused on the unique medical needs of the paediatric patient. Ideally, all communities, hospitals and health regions in Europe should have AMS that serve all patient types, including children. We all have the responsibility to ensure that exis...
    The eradication of smallpox and the elimination of several other infectious diseases from much of the world has provided convincing evidence that vaccines are among the most effective interventions for promoting health. The current... more
    The eradication of smallpox and the elimination of several other infectious diseases from much of the world has provided convincing evidence that vaccines are among the most effective interventions for promoting health. The current scepticism about immunisation among members of the new US administration carries a risk of decreasing immunisation rates also in Europe. While only a small minority of the population are strongly anti-vaccine, their public activities have significantly influenced an uncertainty among the general population about both the safety of and the necessity for vaccination. Therefore, the EAP calls for greater publically available, scientifically supported information on vaccination, particularly targeted at health care providers, for the further development of electronically based immunisation information systems (IIS). We further call on all European countries to work together both in legislative and public health arenas in order to increase vaccination coverage...
    Road traffic accidents are the leading cause of death and disability in children throughout Europe. They remain the leading cause of death among children 5--19 years old in Europe. Children may be injured as pedestrians, bicyclists,... more
    Road traffic accidents are the leading cause of death and disability in children throughout Europe. They remain the leading cause of death among children 5--19 years old in Europe. Children may be injured as pedestrians, bicyclists, motorcyclists or passengers in cars. The European Academy of Pediatrics (EAP) strives to prevent morbidity and death in children. We urge policy-makers to actively work for a "vision zero", where no child is killed in traffic. EAP suggests simple measures such as, secure transport for children between home and school, speed limits, road bumps, wearing bike helmets and seat belts, using child-restraints for small children and enforcement of legislation on road safety.
    Therapeutic hypothermia (TH) has become standard treatment for severe and moderate hypoxic-ischemic neonatal encephalopathy (HIE). Our group has developed an optically based, non-invasive concept of assessing the capacity for oxygen... more
    Therapeutic hypothermia (TH) has become standard treatment for severe and moderate hypoxic-ischemic neonatal encephalopathy (HIE). Our group has developed an optically based, non-invasive concept of assessing the capacity for oxygen delivery from the microcirculation to the cells of a tissue under investigation. The hypothesis was that mechanisms of reduced oxygen delivery due to reduced metabolism in cooled asphyxiated neonates could be characterized with this concept. The skin of 28 asphyxiated newborn infants was studied on days one and three during TH and on day four following rewarming with laser Doppler perfusion measurements (LDPM), computer assisted video microscopy (CAVM) and diffuse reflectance spectroscopy (DRS). Twenty-five healthy neonates served as a control group. The LDPM decreased during cooling (p<0.01). Functional capillary density was higher both during and following TH compared with control infants (p<0.01). Capillary flow velocities were reduced during TH...
    The European Academy of Paediatrics (EAP) is gravely concerned about the human papillomavirus (HPV) vaccination crisis in Japan and particularly about the negative position taken by governmental authorities. Given that the HPV vaccine is... more
    The European Academy of Paediatrics (EAP) is gravely concerned about the human papillomavirus (HPV) vaccination crisis in Japan and particularly about the negative position taken by governmental authorities. Given that the HPV vaccine is both safe and effective, there is no recognizable reason to date to withhold this lifesaving and cost effective public health measure from a population. Therefore, the EAP strongly encourages the Japanese health authorities to actively support HPV vaccination for the future health of their children and adolescents.
    The optimal timing of magnetic resonance imaging (MRI) in encephalopathic infants treated with hypothermia is unknown and this study examined whether early scans differed from later scans. We assessed paired MRI scans carried out on 41... more
    The optimal timing of magnetic resonance imaging (MRI) in encephalopathic infants treated with hypothermia is unknown and this study examined whether early scans differed from later scans. We assessed paired MRI scans carried out on 41 cooled encephalopathic infants at a median of four and 11 days using two scoring systems: the Rutherford injury scores for the basal ganglia and thalami (BGT), white matter and the posterior limb of the internal capsule and the Bonifacio injury scores for the BGT and watershed area. Both systems produced consistent injury severity scores in 37/41 infants on both days, with Rutherford scores predicting poor outcome in six early scans and seven later scans (Kappa 0.91) and Bonifacio doing the same in seven and nine scans (Kappa 0.85). A white matter/watershed score of two or a BGT score of one indicated severe changes by day 11 in three infants but lower scores did not. MRI scans indicated that the Rutherford and Bonifacio systems produced similar score...
    Electroencephalogram (EEG) is commonly used to monitor brain activity in preterm neonates. Long-term EEG is used to predict outcomes by total band power. This study reports effective connectivity analyses in the fronto-parietal network in... more
    Electroencephalogram (EEG) is commonly used to monitor brain activity in preterm neonates. Long-term EEG is used to predict outcomes by total band power. This study reports effective connectivity analyses in the fronto-parietal network in preterm infants. Directed transfer functions (DTFs) were used in fully automated calculations of effective connectivity. Continuous eight-channel EEG recordings were performed for three full days starting at a median of 5.3h (2.5-11.2h) after birth. Analyses were performed using the channels Fp1, Fp2, P3 and P4. DTF were calculated every second in every connection and channel for all frequencies from 1Hz to 30Hz. The median connectivity was used in the connectivity assessment. Parieto-frontal connectivity was significantly higher (0.22) than fronto-parietal connectivity (0.05). There was a significant decrease in parieto-frontal connectivity between day one (0.18) and three. Conversely, there was a significant increase in fronto-parietal connectivi...
    Background: Severe neonatal encephalopathy (NE) of hypoxic-ischaemic origin may cause death or life-long disability. Acute encephalopathy may also affect cerebrovascular control. Pourcelot's cerebrovascular resistance index (RI) ≤0.55... more
    Background: Severe neonatal encephalopathy (NE) of hypoxic-ischaemic origin may cause death or life-long disability. Acute encephalopathy may also affect cerebrovascular control. Pourcelot's cerebrovascular resistance index (RI) ≤0.55 was predictive of poor outcome in normothermic NE infants. Recent studies have questioned its predictive power during therapeutic hypothermia (HT). Objective: To assess the predictive power of RI during HT and after rewarming. Methods: 45 infants with NE treated with HT for 72 h had their RI calculated during early (median 11 h) and late (median 62 h) cooling and after rewarming (median 89 h). Poor outcome was defined as death or abnormalities on day 10 magnetic resonance imaging shown to predict severe neuromotor disability. Results: RI ≤0.55 during cooling did not differentiate between good and poor outcome (late cooling, p = 0.08), but was powerful after rewarming (p = 0.004). RI ≤0.55 predicted true poor outcome in 43% (95% confidence interval ...
    Background: Spectral EEG analysis using automated quantification of total absolute band power (tABP) expresses brain function. We hypothesized that pCO2 or blood glucose affects tABP during the critical first days of life in premature... more
    Background: Spectral EEG analysis using automated quantification of total absolute band power (tABP) expresses brain function. We hypothesized that pCO2 or blood glucose affects tABP during the critical first days of life in premature infants. Objective: To use automated tABP quantification to determine whether EEG background activity in premature infants during the first 3 days of life is influenced by pCO2 or blood glucose levels. Methods: Preterm infants, group 1 [gestational age (GA) = 24-27 weeks] and group 2 (GA = 28-30 weeks), underwent continuous EEG monitoring for 3 days after birth. Biochemical data were extracted from the observational datasheet used during monitoring. Blood samples were taken at the request of the attending physician. Statistical analyses were performed as repeated measurements using linear mixed models with a random intercept. The effect of time was treated as a fixed covariate and the GA groups as a fixed factor in all models. Continuous data were desc...
    Background: Spectral EEG analysis using automated quantification of total absolute band power (tABP) for long-term brain monitoring is reliable. We hypothesised that tABP during the first critical days of life could be a useful tool for... more
    Background: Spectral EEG analysis using automated quantification of total absolute band power (tABP) for long-term brain monitoring is reliable. We hypothesised that tABP during the first critical days of life could be a useful tool for predicting later developmental outcomes. Objective: To determine whether measuring EEG background activity in premature infants with automated tABP quantification during the first 3 days of life correlated with their developmental outcomes at 24 months. Methods: Preterm infants (group 1, gestational age, GA 24–28 weeks and group 2, GA 28–31 weeks) were continuously monitored by EEG for 3 days after birth. Their developmental outcomes were assessed using the Bayley-II and Peabody-2 developmental tests at 24 months. Their respective indices were calculated. Normal (index ≥85) and abnormal (index <85) outcomes were correlated with the tABP. Results: In group 1, the tABP was significantly lower in the abnormal infants than in the normal infants. The s...

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