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Physical activity (PA) is a crucial factor in preventing and treating obesity and related complications. In this one-arm pre–post longitudinal prospective study, we evaluated the effects of a 12-week online supervised training program on cardiac morphology, function and blood pressure (BP) in children with obesity. The training program consisted of three sessions per week, each lasting 60 min. Advanced echocardiographic imaging (tissue Doppler and longitudinal strain analysis) was used to detect subclinical changes in heart function. Categorical variables were described as counts and percentages; quantitative variables as the mean and standard deviation (SD) as they were normally distributed (Shapiro–Wilks test). Pre–post comparisons were made with a paired t-test. A total of 27/38 (71%) enrolled patients (18M/9F, 11 ± 2 years) completed the training protocol and were considered in the analysis. At baseline, no hypertensive patient was noted; all echocardiographic variables were within the normal range. After training, we observed a significant reduction in BP parameters, including systolic BP values and Z-score, diastolic BP values, centiles and Z-score, and mean arterial pressure (all p < 0.05). Significant variations in echocardiographic interventricular septum (IVSd) thickness (p = 0.011), IVSd Z-score (p = 0.001), left ventricular (LV) end-diastolic diameter (p = 0.045), LV posterior wall thickness Z-score (p = 0.017), and LV global longitudinal strain (p = 0.016) were detected. No differences in LV diastolic function and right ventricular strain were noted. PA plays a decisive role in improving BP control and has benefits on left ventricle systolic function, representing a strategic approach to limit CV risk. Online exercise could be an excellent method of training in children with obesity.

OBJECTIVES Right ventricular outflow tract abnormalities (RVOTA) have been mostly reported in recipient twins (RT) of monochorionic/diamniotic (MC/DA) twin pregnancies with twin-to-twin transfusion syndrome (TTTS). Aim of the study was to describe RVOTA detected in MC/DA pregnancies without TTTS. METHODS Cases of RVOTA were retrieved from our database among all MC/DA pregnancies without TTTS from 2009 to 2018. RESULTS Out of 891 MC/DA twin pregnancies without TTTS, 14 (1.6%) were associated with RVOTA: 10 pulmonary stenosis (PS), one steno-insufficiency, one insufficiency and two atresia (PA). In 93% of cases (13/14), pregnancy was complicated either by amniotic fluid discrepancy (AFD) or by TAPS or mostly by selective fetal growth restriction (sFGR) (11/13: 85%), involving predominantly (10/11: 91%) the large twin, with high incidence (9/11: 82%) of sFGR and AFD coexistence. Eight out of 14 (57%) survived after the perinatal period (7 PS, 1 PA). Five (62%) underwent pulmonary balloon valvuloplasty, whereas 3 children still showed persistent mild PS at cardiac follow up after 1 year of life. CONCLUSIONS RVOTA can occur in MC/DA pregnancies without TTTS, particularly when other complications coexist. In complicated cases specialized fetal echocardiographic evaluation is recommended during pregnancy; RVOTA cases should be delivered in a tertiary level center, where cardiologists are available.

Purpose COVID-19 disease may result in a severe multisystem inflammatory syndrome in children (MIS-C), which in turn may alter thyroid function (TF). We assessed TF in MIS-C, evaluating its impact on disease severity. Methods We retrospectively considered children admitted with MIS-C to a single pediatric hospital in Milan (November 2019–January 2021). Non-thyroidal illness syndrome (NTIS) was defined as any abnormality in TF tests (FT3, FT4, TSH) in the presence of critical illness and absence of a pre-existing hormonal abnormality. We devised a disease severity score by combining severity scores for each organ involved. Glucose and lipid profiles were also considered. A principal component analysis (PCA) was performed, to characterize the mutual association patterns between TF and disease severity. Results Of 26 (19 M/7F) patients, median age 10.7 (IQR 5.8–13.3) years, 23 (88.4%) presented with NTIS. A low FT3 level was noted in 15/23 (65.3%), while the other subjects had varying combinations of hormone abnormalities (8/23, 34.7%). Mutually correlated variables related to organ damage and inflammation were represented in the first dimension (PC1) of the PCA. FT3, FT4 and total cholesterol were positively correlated and characterized the second axis (PC2). The third axis (PC3) was characterized by the association of triglycerides, TyG index and HDL cholesterol. TF appeared to be related to lipemic and peripheral insulin resistance profiles. A possible association between catabolic components and severity score was also noted. Conclusions A low FT3 level is common among MIS-C. TF may be useful to define the impact of MIS-C on children’s health and help delineate long term follow-up management and prognosis.

Variants in SCN2A, encoding the voltage-gated sodium channel Nav1.2, are commonly associated with developmental and epileptic encephalopathy. Although animal studies demonstrated a role for Nav1.2 in intraventricular conduction, heart anomalies have been only occasionally described in patients with SCN2A variants. In this report we trace the prenatal and neonatal history of a fetus/newborn with a de novo pathogenic variant in the SCN2A gene identified by prenatal trio whole-exome sequencing (WES). In addition to more typically SCN2A-associated neurological manifestations, the patient showed sustained tachyarrhythmia, potentially expanding the phenotypic spectrum associated with SCN2A variants and raising the question of whether cardiological assessment and prompt pharmacological intervention in SCN2A channelopathies to avoid heart complications might be beneficial. To the best of our knowledge, this represents the first clinical description of a SCN2A phenotype in a prenatal setting, as well as the first SCN2A diagnosis achieved by prenatal trio-WES approach.

Objective We describe a case of severe hypoglycemia in a 14-month-old child as a suspected adverse drug reaction (ADR) to nadolol, and we performed an analysis of the FDA Adverse Event Reporting System (FAERS) database. Although previous reports have identified the risk of severe hypoglycemia in children during treatment with β-blockers, little is known about hypoglycemia as an ADR in infants treated with nadolol. Moreover, the pharmacodynamic and pharmacokinetic profiles of nadolol in children aged less than 1 year old are still not fully known. Materials and methods We extracted all ADR reports involving nadolol from the FAERS database; in order to reduce the risk of bias, we only considered cases that exclusively reported nadolol as the suspect drug. We then selected cases of hypoglycemia in the pediatric population and conducted a manual deduplication. Results Upon FAERS database analysis, a total of 2,674 suspected ADR reports to nadolol were found. Of these, 1,950 (73%) were solely attributed to nadolol, and 63 of them were hypoglycemic events. A total of 47 reports included the relevant pediatric age (74.6%). After deduplication, we identified 25 cases (mean age: 3.65 years old); all of these reports were categorized as serious, and hospitalization was required in 15 cases. Conclusion Hypoglycemia is a reported life-threatening ADR associated with nadolol, especially in infants, in whom this drug should be used with caution.

ObjectiveTo describe neurological involvement in multisystem inflammatory syndrome in children (MIS-C) and to evaluate whether neurological manifestations are related to the degree of multiorgan involvement and inflammation.MethodsThe authors conducted a retrospective analysis of clinical, electroencephalographic (EEG), neuroradiological (MRI), and CSF parameters in 62 children with MIS-C (45 M, age 8 months—17 years, mean age 9 years) hospitalized between October 1, 2020 and March 31, 2022.ResultsNeurological involvement was documented in 58/62 (93.5%) patients. Altered mental status was observed in 29 (46.7%), focal neurological signs in 22 (35.4%), and non-specific symptoms in 54 (87%). EEG was performed in 26/62 children: 20 showed EEG slowing, diffuse or predominantly over the posterior regions. Ten patients underwent brain MRI: three showed a cytotoxic lesion of the corpus callosum. CSF analysis, performed in six patients, was normal. On the basis of the clinical and EEG findings, two profiles of neurological involvement were identified: 16/62 (26%) patients presented encephalitis with rapid-onset encephalopathy, focal neurological signs, and EEG slowing; 42/62 (68%) showed mild neurological involvement with mild or non-specific neurological signs. All patients received intravenous immunoglobulin and methylprednisolone (MTP), low-molecular-weight heparin, and therapeutic-dose anticoagulant treatment. Children with severe encephalopathy received intravenous MTP at 30 mg/kg/day for 3 days, obtaining rapid clinical and EEG improvement. Neurological assessment at discharge was normal in all cases. Children with encephalitis were younger than those without (median age 5 and 10 years, respectively); no differences between the two groups were found in the other parameters: comorbidities, fever, number of organs and systems involved, shock, hospitalization, pediatric intensive care unit admission, non-invasive ventilation, inotropic support, laboratory data.ConclusionNeurological involvement in MIS-C is frequent but not serious in most cases: around two thirds of the affected children had mild and short-lasting symptoms. It seems to be related to age, but not to the degree of multiorgan involvement and inflammation. In children with acute immune-mediated encephalitis, the clinical picture was dominated by encephalopathy that disappeared with immunomodulatory therapy. Neurological assessment allowed timely diagnosis and treatment.

Objective By the end of February 2020, the COVID-19 pandemic infection had spread in Northern Italy, with thousands of patients infected. In Lombardy, the most affected area, the majority of public and private hospitals were dedicated to caring for COVID-19 patients and were organized following the 'Hub-and-Spoke' model for other medical specialties, like cardiac surgery and interventional procedures for congenital cardiac disease (CHD). Here, we report how the congenital cardiac care system was modified in Lombardy and the first results of this organization. Methods We describe a modified 'Hub-and-Spoke' model - that involves 59 birthplaces and three specialized Congenital Cardiac Centers -- and how the hub center organized his activity. We also reported the data of the consecutive cases hospitalized during this period. Results From 9 March to 15 April, we performed: a total of 21 cardiac surgeries, 4 diagnostic catheterizations, 3 CT scans, and 2 CMR. In three cases with prenatal diagnosis, the birth was scheduled. The spoke centers referred to our center six congenital cardiac cases. The postop ExtraCorporeal Membrane Oxygenation support was required in two cases; one case died. None of these patients nor their parents or accompanying person was found to be COVID-19-positive; 2 pediatric intensivists were found to be COVID-19-positive, and needed hospitalization without mechanical ventilation; 13 nurses had positive COVID swabs (4 with symptoms), and were managed and isolated at home. Conclusion Our preliminary data suggest that the model adopted met the immediate needs with a good outcome without increased mortality, nor COVID-19 exposure for the patients who underwent procedures.

Background Multisystem inflammatory syndrome in children (MIS-C) is a novel condition temporally associated with SARS-CoV2 infection. Cardiovascular involvement is mainly evident as acute myocardial dysfunction in MIS-C. The aim of this study was to describe the cardiac dysfunction in patients with MIS-C, defining the role of severity in the clinical presentations and outcomes in a single cohort of pediatric patients. Methods A single-center retrospective study on patients diagnosed with MIS-C, according to the Center for Disease Control and Prevention (CDC) definition, and referred to Vittore Buzzi Children’s Hospital in Milan from November 2020 to February 2021. Patients were managed according to a local approved protocol. According to the admission cardiac left ventricular ejection fraction (LVEF), the patients were divided into group A (LVEF

Background There is mounting evidence on the existence of a Pediatric Inflammatory Multisystem Syndrome-temporally associated to SARS-CoV-2 infection (PIMS-TS), sharing similarities with Kawasaki Disease (KD). The main outcome of the study were to better characterize the clinical features and the treatment response of PIMS-TS and to explore its relationship with KD determining whether KD and PIMS are two distinct entities. Methods The Rheumatology Study Group of the Italian Pediatric Society launched a survey to enroll patients diagnosed with KD (Kawasaki Disease Group – KDG) or KD-like (Kawacovid Group - KCG) disease between February 1st 2020, and May 31st 2020. Demographic, clinical, laboratory data, treatment information, and patients’ outcome were collected in an online anonymized database (RedCAP®). Relationship between clinical presentation and SARS-CoV-2 infection was also taken into account. Moreover, clinical characteristics of KDG during SARS-CoV-2 epidemic (KDG-CoV2) were compared to Kawasaki Disease patients (KDG-Historical) seen in three different Italian tertiary pediatric hospitals (Institute for Maternal and Child Health, IRCCS “Burlo Garofolo”, Trieste; AOU Meyer, Florence; IRCCS Istituto Giannina Gaslini, Genoa) from January 1st 2000 to December 31st 2019. Chi square test or exact Fisher test and non-parametric Wilcoxon Mann-Whitney test were used to study differences between two groups. Results One-hundred-forty-nine cases were enrolled, (96 KDG and 53 KCG). KCG children were significantly older and presented more frequently from gastrointestinal and respiratory involvement. Cardiac involvement was more common in KCG, with 60,4% of patients with myocarditis. 37,8% of patients among KCG presented hypotension/non-cardiogenic shock. Coronary artery abnormalities (CAA) were more common in the KDG. The risk of ICU admission were higher in KCG. Lymphopenia, higher CRP levels, elevated ferritin and troponin-T characterized KCG. KDG received more frequently immunoglobulins (IVIG) and acetylsalicylic acid (ASA) (81,3% vs 66%; p = 0.04 and 71,9% vs 43,4%; p = 0.001 respectively) as KCG more often received glucocorticoids (56,6% vs 14,6%; p Conclusion Our study suggests that SARS-CoV-2 infection might determine two distinct inflammatory diseases in children: KD and PIMS-TS. Older age at onset and clinical peculiarities like the occurrence of myocarditis characterize this multi-inflammatory syndrome. Our patients had an optimal response to treatments and a good outcome, with few complications and no deaths.

Severe acute respiratory syndrome coronavirus 2 infection in children mainly shows a milder course. In complicated cases, it is unknown whether inflammation is predictive of disease severity, as in adults. Moreover, cardiac involvement is anecdotally described. We report the case of a 2-month-old infant with severe acute respiratory syndrome coronavirus 2 infection presenting with fever, tachycardia and elevated interleukin-6, who was diagnosed with myocarditis and treated with immunoglobulins.

The pediatric ultrasound measurement of the inferior vena cava (IVC) and aorta (AO) with the study of the collapsibility index (CI) and of IVC-to-AO ratio (IVC/AO) can provide clinicians in the acute care setting with information on abnormal volume status but one of the major limitations is a lack of reference normal values by body surface area (BSA) and age. The aim of this study was to provide reference ranges for the sonographic measurement of IVC, AO, and IVC/AO ratio in healthy Caucasian Italian children.We enrolled prospectively 516 healthy Caucasian Italian children aged between 1 month and 16 years. Echocardiographic IVC and AO diameters were collected and presented separately for children aged ≤1 year and for children aged over 1 year. For children1 year we categorized subjects into 3 years classes. CI and IVC/AO for the systolic aortic diameter were then calculated. For children over 1 year, age reference ranges were age-related or BSA-related; for children of ≤1 year, reference ranges were determined with their 90% confidence intervals regardless of age and of BSA.Tables and charts with reference ranges for all the echocardiographic measurements are presented for children aged1 year according to age and BSA. The equations to obtain percentile and Z-score for each echocardiographic measurement are provided. The reference ranges for children aged ≤1 year are shown considering the small 90% confidence intervals for upper and lower limits. CI was 30% (SD 17%) in children1 year and 36% (SD 16%) in children1 year. IVC/AOs showed age-dependent values from 0.83 (SD 0.20) age1 year to 1.22 (SD 0.31) in older subjects.We report reliable reference ranges for echocardiographic measurement of IVC, AO, CI, and IVC/AO for a Caucasian Italian healthy pediatric population.

Background: While other viral infections occurring in early pregnancy are known to be associated with fetal cardiac malformations, little is known about CMV and its causative role. Only a few case repots have been described reporting a correlation between congenital CMV infection and cardiac defects.Case-report: We report the case of a 7-day-old neonate who was referred to our Pediatric Infectivology Department for maternal cytomegalovirus (CMV) seroconversion during the first trimester of pregnancy and confirmed congenital infection. At first evaluation, the baby presented with a cardiac murmur and signs of acute heart failure, along with jaundice and hypotonia. At cardiac ultrasound, a perimembranous doubly-committed ventricular septal defect and a reduced aortic isthmus diameter were revealed.Conclusion: Despite further large-scale prospective studies are needed to confirm or rule out this association, CMV DNA urine detection might be worth to be considered as part of the diagnostic process in neonates with isolated heart defects.

A combination of information from blood glucose (BG) and heart rate (HR) measurements has been proposed to investigate the HR changes related to nocturnal hypoglycemia (NH) episodes in pediatric subjects with type 1 diabetes (T1D), examining whether they could improve hypoglycemia prediction. We enrolled seventeen children and adolescents with T1D, monitored on average for 194 days. BG was detected by flash glucose monitoring devices, and HR was measured by wrist-worn fitness trackers. For each subject, we compared HR values recorded in the hour before NH episodes (before-hypoglycemia) with HR values recorded during sleep intervals without hypoglycemia (no-hypoglycemia). Furthermore, we investigated the behavior after the end of NH. Nine participants (53%) experienced at least three NH. Among these nine subjects, six (67%) showed a statistically significant difference between the before-hypoglycemia HR distribution and the no-hypoglycemia HR distribution. In all these six cases, the before-hypoglycemia HR median value was higher than the no-hypoglycemia HR median value. In almost all cases, HR values after the end of hypoglycemia remained higher compared to no-hypoglycemia sleep intervals. This exploratory study support that HR modifications occur during NH in T1D subjects. The identification of specific HR patterns can be helpful to improve NH detection and prevent fatal events.

Background: The aim of the study was to document cardiovascular clinical findings, cardiac imaging and laboratory markers in children presenting with the novel multisystemic inflammatory syndrome associated with COVID-19. Methods: A real-time internet based survey was sent via the member mailing database for Association for European Paediatric and Congenital Cardiologists (AEPC) working groups for Cardiac Imaging and Cardiovascular Intensive Care member. Inclusion criteria was children 0-18 years admitted to hospital between March 1 and June 6, 2020 with diagnosis of an inflammatory syndrome and acute cardiovascular complications. Findings: A total of 286 children from 55 centres from 17 European countries were included. The median age was 8·4 years (IQR 3·8-12·4 years) and 67% were males. Most common cardiovascular complications were shock (40%), cardiac arrhythmias (35%), pericardial effusion (28%) and coronary artery dilatation (24%). Reduced left ventricular ejection fraction was present in 52% of patients and 93% had raised cardiac troponin (cTnT). The biochemical markers of inflammation were raised in majority of patients on admission: elevated CRP (99%), ferritin (79%), procalcitonin (96%), NT-proBNP (93%), IL-6 level (88%) and D-dimers (90%). There was a statistically significant correlation between degree of elevation in cardiac and biochemical parameters and need of intensive care support (p

MIS-C (multisystem inflammatory syndrome in children) linked to SARS-CoV-2 infection, is a pathological state observed in subjects younger than 21 years old with evidence of either current SARS-CoV-2 infection or exposure within the 4 weeks prior to the onset of symptoms, the presence of documented fever, elevated markers of inflammation, at least two signs of multisystem involvement, and, finally, lack of an alternative diagnosis. They share with adult COVID-19 patients the presence of altered markers of inflammation, but unlike most adults the symptoms are not pulmonary but are affecting several organs. Lipid mediators arising from polyunsaturated fatty acids (PUFA) play an important role in the inflammatory response, with arachidonic acid-derived compounds, such as prostaglandins and leukotrienes, mainly pro-inflammatory and ω3 PUFA metabolites such as resolvins and protectins, showing anti-inflammatory and pro-resolution activities. In order to assess potential alterations of these FA, we evaluated the blood fatty acid profile of MIS-C children at admission to the hospital, together with biochemical, metabolic and clinical assessment. All the patients enrolled showed altered inflammatory parameters with fibrinogen, D-dimer, NT-proBNP, ferritin, aspartate aminotransferase (AST), C-reactive protein (CRP) and TrygIndex levels over the reference values in all the subjects under observation, while albumin and HDL-cholesterol resulted below the normal range. Interestingly, linoleic acid (LA), arachidonic acid (AA) and the ω3 PUFA docosahexaenoic acid (DHA) results were lower in our study when compared to relative amounts reported in the other studies, including from our own laboratory. This significant alteration is pointing out to a potential depletion of these PUFA as a result of the systemic inflammatory condition typical of these patients, suggesting that LA- and AA-derived metabolites may play a critical role in this pathological state, while ω3 PUFA-derived pro-resolution metabolites in these subjects may not be able to provide a timely, physiological counterbalance to the formation of pro-inflammatory lipid mediators. In conclusion, this observational study provides evidence of FA alterations in MIS-C children, suggesting a significant contribution of ω6 FA to the observed inflammatory state, and supporting a potential dietary intervention to restore an appropriate balance among the FAs capable of promoting the resolution of the observed inflammatory condition.

The competitive binding between CpG-ODN (single-stranded DNA from pathogens) and HLA-B and HLA-A ligands for the inhibitory Killer Immunoglobulin-like Receptors (KIR)3DL1/2 may lead to possible hypo-sensing of pathogens and ineffective clearance. We observed an overabundance of HLA ligands for inhibitory KIR with three domains in KD subjects.

An interaction between metabolic glucose impairment and coronavirus disease 2019 is reported. The development of a severe multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 infection has been described. We evaluated the impact of MIS-C on glycemic patterns in pediatric patients. A group of 30 children and adolescents affected by MIS-C were considered; all patients were normal weight. Clinical and biochemical assessments, including surrogate markers of insulin resistance (IR) such as homeostasis model analysis-IR (HOMA-IR) and triglyceride–glucose (TyG) indexes, were recorded. Patients were also invited to undergo an intermittently scanned continuous glucose monitoring (isCGM). HOMA-IR index was calculated in 18 patients (60%), of which 17 (94%) revealed a pathological value. TyG index was computed for all patients and pathological values were detected in all cases. In 15 patients, isCGM data were recorded on average for 9 days (±3 days). Overall, average glucose was 105 mg/dL (±16 mg/dL) and average time spent in the 70–180 mg/dL range (TIR) was 93.76%, with nearly 10% of glucose readings in the 141–180 mg/dL range; glycemic fluctuations over the hyperglycemic threshold were detected in four patients. Regular glucose monitoring may be useful to prevent metabolic imbalance and obtain a better outcome.

Clonal endothelial progenitor cells (EPCs) have been implicated in the aberrant vascular growth that features infantile hemangioma (IH), the most common benign vascular tumor in childhood that may cause ulceration, bleeding, and/or permanent disfigurement. Endothelial colony-forming cells (ECFCs), truly endothelial EPCs endowed with clonal ability and capable of forming patent vessels in vivo, remodel their Ca(2+) toolkit in tumor-derived patients to acquire an adaptive advantage. Particularly, they upregulate the proangiogenic store-operated Ca(2+) entry (SOCE) pathway due to the overexpression of its underlying components, that is, stromal interaction molecule 1 (Stim1), Orai1, and transient receptor potential canonical 1 (TRPC1). The present work was undertaken to assess whether and how the Ca(2+) signalosome is altered in IH-ECFCs by employing Ca(2+) and nitric oxide (NO) imaging, real-time polymerase chain reaction, western blotting, and functional assays. IH-ECFCs display a lower intracellular Ca(2+) release in response to either pharmacological (i.e., cyclopiazonic acid) or physiological (i.e., ATP and vascular endothelial growth factor) stimulation. Conversely, Stim1, Orai1, and TRPC1 transcripts and proteins are normally expressed in these cells and mediate a constitutive SOCE, which is sensitive to BTP-2, La(3+), and Pyr6 and recharges the intracellular Ca(2+) pool. The resting SOCE in IH-ECFCs is also associated to an increase in their proliferation rate and the basal production of NO compared to normal cells. Likewise, the pharmacological blockade of SOCE and NO synthesis block IH-ECFC growth. Collectively, these data indicate that the constitutive SOCE activation enhances IH-ECFC proliferation by augmenting basal NO production and sheds novel light on the molecular mechanisms of IH.

The primary purpose of these practical guidelines related to Kawasaki disease (KD) is to contribute to prompt diagnosis and appropriate treatment on the basis of different specialists’ contributions in the field. A set of 40 recommendations is provided, divided in two parts: the first describes the definition of KD, its epidemiology, etiopathogenetic hints, presentation, clinical course and general management, including treatment of the acute phase, through specific 23 recommendations. Their application is aimed at improving the rate of treatment with intravenous immunoglobulin and the overall potential development of coronary artery abnormalities in KD. Guidelines, however, should not be considered a norm that limits treatment options of pediatricians and practitioners, as treatment modalities other than those recommended may be required as a result of peculiar medical circumstances, patient’s condition, and disease severity or complications.

Kawasaki disease (KD) is a pediatric acute multisystemic vasculitis complicated by development of coronary artery lesions. The breakthrough theory on KD etiopathogenesis points to pathogens/environmental factors triggered by northeastern wind coming from China. Natural Killer cells and T lymphocytes express the inhibitory/activating Killer Immunoglobulin-like Receptors (KIR) to elicit an immune response against pathogens by binding to human leukocyte antigens (HLA) class I epitopes. We first report on the role of KIR/HLA genetic epistasis in a sample of 100 Italian KD children. We genotyped KIR, HLA-A, HLA-B and HLA-C polymorphisms, and compared KD data with those from 270 Italian healthy donors. The HLA-A*11 ligand for KIR2DS2/2DS4/3DL2 was a KD susceptibility marker by itself (odds ratio (OR)=3.85, confidence interval (CI)=1.55-9.53, P=0.004). Although no epistasis between HLA-A*11 and KIR2DS2/S4 emerged, HLA-A*11 also engages KIR3DL2, a framework gene encoding for a pathogen sensor of CpG-oligodeoxynucleotides (CpG-ODN), and KD blood mononuclear cells are actually prone to pathogen CpG-ODN activation in the acute phase. Moreover, carriers of KIR2DS2/HLA-C1 and KIR2DL2/HLA-C1 were more frequent among KD, in keeping with data demonstrating the involvement of these HLA/KIR couples in autoimmune endothelial damage. The highest KD risk factor was observed among carriers of KIR2DL2 and two or more HLA ligands (OR=10.24, CI=1.87-56.28; P=0.007).

Vascular rings are congenital anomalies that lead to variable degrees of respiratory problems or feeding difficulties by forming a complete or partial ring compressing the trachea, the bronchi, and the esophagus. The clinical diagnosis of vascular rings is often challenging for the pediatrician because the clinical manifestations are heterogeneous and nonspecific. Symptoms can vary from wheezing, stridor, dyspnea, and/or dysphagia to life-threatening conditions; however, they may not be present. The aim of this study is to review the recent literature on this subject and describe new developments in diagnostics and imaging.

Noncompaction cardiomyopathy is a rare disorder, often associated with cardiac and noncardiac malformations. Hirschsprung's disease, a well-known aganglionosis, is associated with congenital heart diseases and has been reported to be due to impairment migration and differentiation of neural crest cells. Here, we present an 8-month-old male infant who died for cardiogenic shock after surgical resection of the involved bowel segment. The child was affected by both noncompaction cardiomyopathy and Hirschsprung's disease, two entities which can share a common neural crest-derived etiology.

Pulmonary atresia with intact ventricular septum (PAIVS) is a morphologically heterogeneous lesion characterized by variable dimensions of the right ventricle (RV) from a normal size to a variable degree of hypoplasia, often with associated anomalies of the coronary circulation. Critical pulmonary stenosis (CPS), also, is often present with an abnormal right ventricle.

To evaluate and compare cardiovascular adaptation of 36 preterm and 34 fullterm newborns, we analyzed BNP concentration and echocardiographic parameters at day 3 of life and at day 28 (+/-2). On day 3 BNP concentrations (pg/ml) resulted higher in PDA preterm group (n=11; 125, IQR 56.1-301) than preterm without PDA (n=25; 25.5 IQR 10.9-49; p

Background— The prevalence of genetic arrhythmogenic diseases is unknown. For the long-QT syndrome (LQTS), figures ranging from 1:20 000 to 1:5000 were published, but none was based on actual data. Our objective was to define the prevalence of LQTS. Methods and Results— In 18 maternity hospitals, an ECG was performed in 44 596 infants 15 to 25 days old (43 080 whites). In infants with a corrected QT interval (QTc) >450 ms, the ECG was repeated within 1 to 2 weeks. Genetic analysis, by screening 7 LQTS genes, was performed in 28 of 31 (90%) and in 14 of 28 infants (50%) with, respectively, a QTc >470 ms or between 461 and 470 ms. A QTc of 451 to 460, 461 to 470, and >470 ms was observed in 177 (0.41%), 28 (0.06%), and 31 infants (0.07%). Among genotyped infants, disease-causing mutations were found in 12 of 28 (43%) with a QTc >470 ms and in 4 of 14 (29%) with a QTc of 461 to 470 ms. One genotype-negative infant (QTc 482 ms) was diagnosed as affected by LQTS on clinical grounds. Among family members of genotype-positive infants, 51% were found to carry disease-causing mutations. In total, 17 of 43 080 white infants were affected by LQTS, demonstrating a prevalence of at least 1:2534 apparently healthy live births (95% confidence interval, 1:1583 to 1:4350). Conclusions— This study provides the first data-based estimate of the prevalence of LQTS among whites. On the basis of the nongenotyped infants with QTc between 451 and 470 ms, we advance the hypothesis that this prevalence might be close to 1:2000. ECG-guided molecular screening can identify most infants affected by LQTS and unmask affected relatives, thus allowing effective preventive measures.

We evaluated the correlation between brain natriuretic peptide (BNP) in umbilical cord blood after normal pregnancy, in blood samples of twenty-nine Italian healthy newborns and paired echocardiographic parameters. Plasma BNP was evaluated in UCB (T0) and in blood on day 3 (T1), 30 (T2) of life. Echocardiographic parameters were recorded at T1 and T2. Median of BNP concentrations in cord blood was 8.6 pg/ml. Median BNP concentrations on T1 was 59.2 pg/ml, on T2 was 8.7 pg/ml. Significantly higher BNP concentrations were reported on T1 than T0 and T2 (p0.0001), while no significant difference resulted between T0 and T2. Plasma BNP at T2 was significantly correlated with mVTI (p=0.006), E wave (p=0.004), LA (p=0.047), LVPW (p=0.004), M (p=0.025). No correlation was found with SF% and E/A. Our results confirm that in healthy and term neonates the cord blood BNP concentrations are low. On T1 BNP values are high with wide ranges because of physiological adjustment to postnatal circulation. When echocardiographic parameters are in normal ranges, BNP concentrations return to low levels on day 30. In healthy newborns left ventricular filling, LA size and M seem to influence BNP levels rather than left ventricular systolic and diastolic function.