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1.  Relationship between clinical sinusitis symptoms and sinus CT severity in pediatric post bone marrow transplant and immunocompetent patients 
European journal of pediatrics  2011;171(2):375-381.
Since typical inflammatory responses may be diminished in children following bone marrow transplant (BMT), computed tomography (CT) imaging of the sinuses has been increasingly ordered to diagnose sinusitis in this group. The objective of this study was to determine the association between clinical sinusitis symptoms and sinus opacification on CT scans in post BMT versus immunocompetent children. Our sample was comprised of 64 post BMT and 86 immunocompetent children with sinus CT scans. CT sinus opacification was scored using the modified Lund–Mackay staging system. The relationship between clinical sinusitis symptoms (rhinorrhea, nasal congestion, cough, headache, and facial pain) and opacification was compared for the two groups. The severity of sinus opacification in the BMT group was significantly higher compared to the immunocompetent group. In combined patient groups the odds ratio (OR) for moderate/severe sinusitis was significantly elevated for rhinorrhea (OR=3.00; 95% confidence interval [CI], 1.27–7.12), cough (OR=2.80; 95% CI, 1.22–6.42), and having either rhinorrhea, nasal congestion, or cough (OR= 4.76; 95% CI, 1.71–13.24). While the immunocompetent group had a greater number of sinusitis symptoms compared to the post BMT group, both groups had a significant increase in the severity on CT with increasing number of symptoms.
Conclusion
In post BMT patients, our data demonstrated higher odds of moderate/severe sinusitis on CT scans associated with rhinorrhea, cough or nasal congestion. These finding suggest that in post BMT children, detailed sinus history may still play a vital role in the diagnosis of sinusitis.
doi:10.1007/s00431-011-1560-0
PMCID: PMC4234098  PMID: 21904829
Sinusitis; Children; Bone marrow transplant; Computed tomography; Paranasal sinuses; Symptoms
2.  Cow’s milk allergy: evidence-based diagnosis and management for the practitioner 
European Journal of Pediatrics  2014;174:141-150.
This review summarizes current evidence and recommendations regarding cow’s milk allergy (CMA), the most common food allergy in young children, for the primary and secondary care providers. The diagnostic approach includes performing a medical history, physical examination, diagnostic elimination diets, skin prick tests, specific IgE measurements, and oral food challenges. Strict avoidance of the offending allergen is the only therapeutic option. Oral immunotherapy is being studied, but it is not yet recommended for routine clinical practice. For primary prevention of allergy, exclusive breastfeeding for at least 4 months and up to 6 months is desirable. Infants with a documented hereditary risk of allergy (i.e., an affected parent and/or sibling) who cannot be breastfed exclusively should receive a formula with confirmed reduced allergenicity, i.e., a partially or extensively hydrolyzed formula, as a means of preventing allergic reactions, primarily atopic dermatitis. Avoidance or delayed introduction of solid foods beyond 4–6 months for allergy prevention is not recommended.
Conclusion: For all of those involved in taking care of children’s health, it is important to understand the multifaceted aspects of CMA, such as its epidemiology, presentation, diagnosis, and dietary management, as well as its primary prevention.
doi:10.1007/s00431-014-2422-3
PMCID: PMC4298661  PMID: 25257836
Allergy; Children; Infants; Pediatrics
3.  Three novel mutations of the G6PC gene identified in Chinese patients with glycogen storage disease type Ia 
Glycogen storage disease type Ia (GSDIa) is an autosomal recessively inherited disease characterized by poor tolerance to fasting, growth retardation, and hepatomegaly resulting from accumulation of glycogen and fat in the liver. Germline mutations of glucose-6-phosphatase (G6PC) gene have been identified as a cause of GSDIa. In this study, we performed mutation analysis in five Chinese GSDIa patients belonging to five unrelated families by direct DNA sequencing. All patients were clinically classified as GSDIa. Mutation analysis of the G6PC gene revealed that all patients carried biallelic G6PC mutations (p.Ile341Asn, p.Ala274Val, p.Phe80Ile, p.Gly118Asp, p.Arg83His, c.262delG, and c.648G>T). Of the seven different mutations identified, three were found to be novel. All of the novel mutations were missense (p.Ala274Val, p.Phe80Ile, and p.Gly118Asp). The c.262delG mutation which leads to a frame-shift and truncated forms of glucose-6-phosphatase was present in three unrelated patients (one homozygote and two heterozygotes). Conclusion: By direct DNA sequencing, three novel G6PC variations were identified which expanded the G6PC mutation spectrum, and provided conclusive genetic evidences for the definitive diagnosis of the Chinese patients.
doi:10.1007/s00431-014-2354-y
PMCID: PMC4289013  PMID: 24980439
GSDIa; Glucose-6-phosphatase; Germline mutation
4.  Prediction of the risk of coronary arterial lesions in Kawasaki disease by serum 25-hydroxyvitamin D3 
European Journal of Pediatrics  2014;173(11):1467-1471.
Kawasaki disease (KD) is associated with the development of coronary arterial lesions (CALs) in children. We aimed to test the hypothesis that circulating 25-hydroxyvitamin D3 [25-(OH)D3] could be identified as a clinical parameter for predicting CALs secondary to KD in children. We enrolled 35 children with KD in the acute phase and measured serum 25-(OH)D3 levels in all of them, then followed up by echocardiography for CALs. Additionally, serum 25-(OH)D3 levels were obtained in 23 febrile children with respiratory tract infections and 30 healthy children. Of the 35 KD children, nine had CALs according to echocardiography and 26 did not (NCALs). Serum 25-(OH)D3 levels were not significantly different between NCALs and healthy children (49.2 ± 23.8 versus 44.1 ± 30.2 ng/ml; P = 0.49). Serum 25-(OH)D3 levels were significantly higher in children with CALs than those without CALs (83.9 ± 26.3 versus 49.2 ± 23.8 ng/ml; P = 0.001). The cutoff value of 65 ng/ml to predict subsequent CALs had a specificity of 0.73, sensitivity of 0.78, and diagnostic accuracy of 0.74. Conclusion: Serum 25-(OH)D3 levels were elevated dur-ing the acute phase in KD children who had subsequent CALs. Serum 25-(OH)D3 levels in the acute phase of KD may be used to predict subsequent CALs.
doi:10.1007/s00431-014-2346-y
PMCID: PMC4194745  PMID: 24889335
Kawasaki disease; 25-Hydroxyvitamin D3; Coronary artery lesions
5.  Infantile Hemangiomas and Retinopathy of Prematurity: Clues to the Regulation of Vasculogenesis 
European journal of pediatrics  2013;172(6):803-809.
Retinopathy of prematurity (ROP) and infantile hemangiomas are vascular disorders that may share common mechanisms. This study examined a potential clinical association between these disorders in populations of preterm infants at two hospitals in the U.S. and Hungary. Clinically collected data from infants with gestational ages less than 32 weeks born between May 1, 2007 and December 31, 2010 seen in the University of Iowa Children’s Hospital or the Department of Obstetrics and Gynecology, University of Pécs, were abstracted from electronic medical records and entered into a study database. Demographic and clinical variables were examined as potential covariates to the disorders of interest. Data were initially analyzed by center and then combined through meta-analysis. Six hundred eighty-four subjects were studied, 236 from Pécs and 448 from Iowa. There were no significant demographic differences between populations. Univariate analysis on each study population yielded covariates to ROP in each population, including infantile hemangioma, which were entered into a logistic regression model. These models were combined through random effects meta-analysis and demonstrated a significant relationship between infantile hemangioma and ROP (odds ratio=1.84, 95% confidence interval 1.08–3.12).
Conclusion
Infantile hemangioma and ROP co-occur in premature infant populations. Further studies are needed to investigate the pathogenesis of both disorders.
doi:10.1007/s00431-013-1966-y
PMCID: PMC3664111  PMID: 23408311
Angiogenesis; Hemangioma; Preterm infants; Retinopathy of prematurity; Vascular endothelial growth factor; Vasculogenesis
7.  The efficacy of Lactobacillus reuteri DSM 17938 in infants and children: a review of the current evidence 
European Journal of Pediatrics  2014;173(10):1327-1337.
We aimed to systematically evaluate evidence on the effectiveness of Lactobacillus reuteri DSM 17938 (L. reuteri) for treating and preventing diseases in infants and children. MEDLINE and the Cochrane Library were searched in December 2013, with no language restrictions, for relevant randomized controlled trials (RCTs) and meta-analyses. The search was updated in April 2014. One systematic review and 14 RCTs met the inclusion criteria. The use of L. reuteri may be considered in the management of acute gastroenteritis as an adjunct to rehydration. There is some evidence that L. reuteri is effective in reducing the incidence of diarrhea in children attending day care centers. There is no evidence of effectiveness of L. reuteri in preventing nosocomial diarrhea in children. The administration of L. reuteri is likely to reduce crying time in infants with infantile colic in exclusively or predominantly exclusively breast-fed infants, but not in formula-fed infants. More studies are needed. Preliminary data suggest that L. reuteri may be effective in the prevention of some functional gastrointestinal disorders, such as colic and regurgitation. This innovative approach needs further evaluation by an independent research team. Preliminary evidence provides a rationale for further assessing the efficacy of L. reuteri for treating functional constipation or functional abdominal pain. However, it is too soon to recommend the routine use of L. reuteri for these conditions. There are no safety concerns with regard to the use of L. reuteri in nonimmunocompromised subjects. There are also data to support the safety of using L. reuteri in preterm infants. Conclusion: Our results precisely define current evidence on the effects of the administration of L. reuteri DSM 17938 to the pediatric population.
doi:10.1007/s00431-014-2328-0
PMCID: PMC4165878  PMID: 24819885
Probiotics; Randomized controlled trial; Systematic review
8.  Clinical practice 
European journal of pediatrics  2010;170(6):681-688.
The incidence of urolithiasis in children is increasing. Adequate knowledge of treatment modalities and surgical options is therefore essential for every pediatrician. Surgical approaches to urolithiasis in children continue to evolve with advancements in technology and sophistication of current equipment and techniques. Perhaps the most significant development in new techniques is the advent of robotic-assisted laparoscopy. This review, for the general pediatrician, summarizes the most recent pediatric data and guidelines for surgical approaches to treatment of urolithiasis.
doi:10.1007/s00431-010-1373-6
PMCID: PMC4011548  PMID: 21190040
Urolithiasis; Pediatrics; Surgery; Endoscopy
9.  Serious Aortic Complications in a Patient with Turner Syndrome 
European journal of pediatrics  2012;172(5):703-705.
An asymptomatic young woman was discovered to have life-threatening aneurysms and dissection of the thoracic aorta during routine evaluation in a Turner syndrome (TS) study. The presence of a heart murmur and hypertension had led to diagnosis and surgical repair of an atrial septal defect at age 5 and of aortic coarctation at age 12 years. The diagnosis of TS was made at age 16 year due to short stature and delayed pubertal development. She was treated with growth hormone from age 16–18 year, and with atenolol, thyroid hormone and estrogen. She discontinued her medications and was lost to medical follow-up at age 20 year. On presenting here at age 26 year, she reported a very active lifestyle, including vigorous exercise and an acting career, with no symptoms of chest or back pain or shortness of breath. Cardiovascular imaging revealed aortic regurgitation, an unsuspected dissection of a severely dilated ascending aorta, and a large descending aortic aneurysm. She required surgical replacement of her aortic valve and ascending aorta, followed by endovascular repair of the descending aortic aneurysm. Conclusion: This patient illustrates the importance of considering the diagnosis of TS in girls with congenital aortic defects and the absolute necessity for close, expert follow-up of these patients who are at high risk for complications after surgical repair due to an underlying aortopathy, hypertension and metabolic disorders. This patient also emphasizes the need to publicize and follow screening guidelines as an increasing number of patients with congenital defects transition to adult care.
doi:10.1007/s00431-012-1808-3
PMCID: PMC3538087  PMID: 22923005
aortic dissection; X chromosome; hypoplastic aorta; congenital heart defect
10.  Hypermethylation of the enolase gene (ENO2) in autism 
European Journal of Pediatrics  2014;173(9):1233-1244.
It has been hypothesized that dysregulation of brain-expressed genes is the major predisposing underlying mechanism for autism. This dysregulation may be mediated by differential methylation of CpG sites within gene promoters, which could be candidate biomarkers and used for early clinical screening of autism. A total of 131 pairs of age- and sex-matched autistic and control subjects were recruited in this study. Peripheral blood cells were analyzed. The first five pairs were randomly applied to array-based genome-wide methylation studies. A neuron-specific gene, ENO2, was found to be hypermethylated in the autistic samples. This difference was validated by bisulfite sequencing PCR (BSP). The differential expression of ENO2 gene was further analyzed with RT-qPCR and ELISA. The hypermethylation of ENO2 within the promoter region was confirmed by BSP to be present in 14.5 % (19/131) of the total of the autistic samples. The mean ENO2 RNA level in these 19 autistic samples was reduced by about 70 % relative to that in controls. The average level of ENO2 protein expression in the 19 autistic samples (15.18 ± 3.51 μg/l) was about half of that in the controls (33.86 ± 8.16 μg/l). Conclusion: These findings suggest that reduced ENO2 expression may be a biomarker for a subset of autistic children.
Electronic supplementary material
The online version of this article (doi:10.1007/s00431-014-2311-9) contains supplementary material, which is available to authorized users.
doi:10.1007/s00431-014-2311-9
PMCID: PMC4134484  PMID: 24737292
Autism; Neurodevelopment; Gene ENO2; Methylation; Epigenetics
11.  Safety and tolerance of a new extensively hydrolyzed rice protein-based formula in the management of infants with cow’s milk protein allergy 
European Journal of Pediatrics  2014;173(9):1209-1216.
Guidelines recommend the use of extensively hydrolyzed cow’s milk protein-based formulas (eHF) in the treatment of infants with cow’s milk protein allergy (CMPA). Extensively hydrolyzed rice protein infant formula (eRHF) has recently become available and could offer a valid alternative. A prospective trial was performed to evaluate the hypo-allergenicity and safety of a new eRHF in infants with a confirmed CMPA. Patients were fed the study formula for 6 months. Clinical tolerance of the eRHF was evaluated with a symptom-based score (SBS) and growth (weight and length) was monitored. Forty infants (mean age, 3.4 months; range, 1–6 months) with CMPA confirmed by a food challenge were enrolled. All infants tolerated the eRHF and the SBS significantly decreased as of the first month of intervention. Moreover, the eRHF allowed a catch-up to normal weight gain as of the first month as well as a normalization of the weight-for-age, weight-for length, and BMI z-scores within the 6-month study period. Conclusion: In accordance with current guidelines, this eRHF was tolerated by more than 90 % of children with proven CMPA with a 95 % confidence interval. This eRHF is an adequate and safe alternative to cow milk-based eHF.
doi:10.1007/s00431-014-2308-4
PMCID: PMC4134482  PMID: 24723091
Cow’s milk protein allergy; Extensive hydrolysate; Extensively hydrolyzed rice protein formula
12.  Clinical and molecular characteristics of two transaldolase-deficient patients 
European Journal of Pediatrics  2014;173(12):1679-1682.
Transaldolase (TALDO) deficiency is a rare metabolic disease in the pentose phosphate pathway, which manifests as a severe, early-onset multisystem disease. The body fluids of affected patients contain increased polyol concentrations and seven-carbon chain carbohydrates. We report the molecular and clinical findings in two recently diagnosed transaldolase-deficient children, both presented at birth. During infancy, they presented thin skin with a network of visible vessels, spider telangiectasias and multiple haemangiomas. Such unusual skin changes are characteristic of liver damage. Later, the patients developed rapidly progressive nodular liver fibrosis, tubulopathy and severe clotting disturbances. The clinical features of these patients were in line with previously studied patients with transaldolase deficiency. The diagnosis was established by detecting high concentrations of erythritol, ribitol, arabitol, sedoheptitol, perseitol, sedoheptulose and sedoheptulose-7-phosphate in the urine. Detection was made by gas chromatography and liquid chromatography-tandem mass spectrometry and then confirmed by molecular analysis of the TALDO gene. Conclusion: Transaldolase deficiency, a rare early-onset multisystem disease, should be considered by neonatologists, paediatricians, hepatologists and nephrologists in the differential diagnosis of patients presenting hepatosplenomegaly, thrombocytopenia, anaemia, bleeding diathesis, liver failure and tubulopathy.
doi:10.1007/s00431-014-2261-2
PMCID: PMC4245499  PMID: 24497183
Transaldolase deficiency; Polyol concentration; Seven-carbon chain carbohydrates; Pentose phosphate pathway
13.  International survey on diagnosis and management of hypotension in extremely preterm babies 
European Journal of Pediatrics  2014;173(6):793-798.
Hypotension is a commonly diagnosed and treated complication of extremely low gestational age newborns (ELGAN), but enormous variation in diagnosis, management and clinical practice has been documented. We sought to evaluate practice regarding the management of hypotension in ELGANs and developed a web-based questionnaire addressing diagnosis, intervention thresholds and modes of treatment of hypotension in ELGANs. We received 216 completed questionnaires from respondents in 38 countries. Most responses (83 %) were from specialist units where, together, over 26,000 very low birth weight (VLBW) infants are cared for annually. The majority (73 %) defined hypotension as a mean blood pressure (BP) in mmHg less than the gestational age in weeks. Sixty percent assessed the circulation with additional methods; echocardiography was the most commonly used (74 %), with left ventricular output and fractional shortening the two most common measurements made. The majority (85 %) used volume administration as the initial intervention. Dopamine was the inotrope most commonly used initially (80 %). If the initial inotrope therapy failed, dobutamine was the most popular second-line treatment (28 %). Delayed cord clamping was used at 51 % of the centres. Conclusion: The definition of hypotension in ELGANs continues to follow traditional standards. Functional echocardiography is now used to assess the circulation at many centres. Volume expansion and dopamine remain the most frequently used therapies.
Electronic supplementary material
The online version of this article (doi:10.1007/s00431-013-2251-9) contains supplementary material, which is available to authorized users.
doi:10.1007/s00431-013-2251-9
PMCID: PMC4032643  PMID: 24390060
Diagnosis; Extremely low gestational age; Hypotension; Survey; Treatment
14.  Towards a safety net for management of 22q11.2 deletion syndrome: guidelines for our times 
European Journal of Pediatrics  2014;173(6):757-765.
The commonest autosomal deletion, 22q11.2 deletion syndrome (22q11DS) is a multisystem disorder varying greatly in severity and age of identification between affected individuals. Holistic care is best served by a multidisciplinary team, with an anticipatory approach. Priorities tend to change with age, from feeding difficulties, infections and surgery of congenital abnormalities particularly of the heart and velopharynx in infancy and early childhood to longer-term communication, learning, behavioural and mental health difficulties best served by evaluation at intervals to consider and initiate management. Regular monitoring of growth, endocrine status, haematological and immune function to enable early intervention helps in maintaining health. Conclusion: Guidelines to best practice management of 22q11DS based on a literature review and consensus have been developed by a national group of professionals with consideration of the limitations of available medical and educational resources.
doi:10.1007/s00431-013-2240-z
PMCID: PMC4032642  PMID: 24384789
22q11 deletion syndrome; Guidelines; Di George; Velocardiofacial; Congenital abnormalities; Resource management
15.  Neuroleptic malignant syndrome in an adolescent with CYP2D6 deficiency 
European Journal of Pediatrics  2013;173(12):1639-1642.
We describe a patient with dystonia and psychotic symptoms treated with standard doses of antipsychotics, who developed neuroleptic malignant syndrome (NMS). A 16-year-old male with a history of misuse of dextromethorphan and pseudoephedrine for recreational purpose presented with dystonia and a psychotic episode. Following continuous treatment with olanzapine (10 mg/day), repeated injections of levomepromazine (37.5 mg/day), and a single injection of haloperidol (2.5 mg), the patient developed NMS. Muscular rigidity, fever (up to 41 °C), hypotension (100/70 mmHg), tachycardia (120 beats per minute), tachypnea (26 breaths per minute), elevated leukocyte count (up to 16.6 × 103/μL), and elevated serum creatinine phosphokinase (CPK) (up to 15,255 U/L) were observed. A diagnosis of NMS was made according to the DSM-IV TR criteria. Genotyping revealed that he was homozygous for a non-functional CYP2D6*4 allele. The case highlights the importance of therapeutic drug monitoring in identification and differentiation of drug-induced effects in psychiatric disorder to prevent NMS and its complications. In addition, genotyping of CYP2D6 might be considered in patients with symptoms suggestive of drug toxicity who are treated with neuroleptics metabolized via the CYP2D6 pathway, as carriage of one or more non-functional alleles may increase the risk for adverse reactions, such as NMS.
doi:10.1007/s00431-013-2208-z
PMCID: PMC4245487  PMID: 24253372
Adverse drug reactions; Pharmacogenetics; CYP2D6; Poor metabolizer; Neuroleptic malignant syndrome
16.  Clinically mild encephalitis/encephalopathy with a reversible splenial lesion associated with febrile urinary tract infection 
European Journal of Pediatrics  2013;173(4):533-536.
Common pathogens of clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) are viruses, such as influenza virus. However, bacteria are rare pathogens for MERS. We report the first patient with MERS associated with febrile urinary tract infection. A 16-year-old lupus patient was admitted to our hospital. She had fever, headache, vomiting, and right back pain. Urinary analysis showed leukocyturia, and urinary culture identified Klebsiella pneumoniae. Cerebrospinal fluid examination and brain single-photon emission computed tomography showed no abnormalities. Therefore, she was diagnosed with febrile urinary tract infection. For further examinations, 99mTc-dimercaptosuccinic acid renal scintigraphy showed right cortical defects, and a voiding cystourethrogram demonstrated right vesicoureteral reflux (grade II). Therefore, she was diagnosed with right pyelonephritis. Although treatment with antibiotics administered intravenously improved the fever, laboratory findings, and right back pain, she had prolonged headaches, nausea, and vomiting. T2-weighted, diffusion-weighted, and fluid attenuated inversion recovery images in brain magnetic resonance imaging showed high intensity lesions in the splenium of the corpus callosum, which completely disappeared 1 week later. These results were compatible with MERS. To the best of our knowledge, our patient is the first patient who showed clinical features of MERS associated with febrile urinary tract infection. Conclusion: In patients with pyelonephritis and an atypical clinical course, such as prolonged headache, nausea, vomiting, and neurological disorders, the possibility of MERS should be considered.
doi:10.1007/s00431-013-2199-9
PMCID: PMC3951960  PMID: 24221606
Bacteria; Febrile urinary tract infection; MERS; Pyelonephritis; Systemic lupus erythematosus
17.  Pediatric non-alcoholic fatty liver disease: an increasing public health issue 
European Journal of Pediatrics  2013;173(2):131-139.
Non-alcoholic fatty liver disease (NAFLD) is a multifactorial condition that encompasses a wide spectrum of liver abnormalities ranging from simple liver steatosis to steatohepatitis (non-alcoholic steatohepatitis), which may be associated with fibrosis and progress to cirrhosis and end-stage liver disease. NAFLD has recently become the most common cause of chronic liver disease in children and adolescents. NAFLD prevalence, alongside obesity, continues to increase among pediatric patients. Obesity is believed to represent a major risk factor for NAFLD, which is considered to be the liver presentation of the metabolic syndrome. Although the pathogenesis of NAFLD is not fully understood, the notion that multiple factors affect disease development and progression is widely accepted. Both genetic background and environmental factors contribute to NAFLD development. A more complete understanding of the pathogenesis may aid in developing non-invasive diagnostic tools and identifying new therapeutic targets. Liver biopsy currently remains the gold standard for NAFLD diagnosis and staging. Although lifestyle and diet modifications are key in NAFLD treatment, the development of new pharmacological therapies is crucial for patients who are unresponsive to first-line therapy. Conclusion: Pediatric NAFLD is an increasing public health issue that remains underdiagnosed. A large-scale screening in the high-risk population, especially among the overweight pediatric patients, should be considered, including measurement of serum transaminases and liver ultrasound. It is crucial to treat this condition as soon as possible in order to avoid the progression to end-stage liver disease.
doi:10.1007/s00431-013-2157-6
PMCID: PMC3929043  PMID: 24068459
Liver fibrosis; Non-alcoholic fatty liver disease; Pediatric patients; Steatohepatitis
18.  ActiTrainer-determined segmented moderate-to-vigorous physical activity patterns among normal-weight and overweight-to-obese Czech schoolchildren 
European Journal of Pediatrics  2013;173(3):321-329.
This study uncovered the patterns of moderate-to-vigorous physical activity (MVPA) in normal-weight and overweight/obese children before, during, and after school lessons. ActiTrainer-based MVPA was assessed over 2 school days (with and without a physical education lesson [PEL] in a sample of three hundred thirty-eight 9- to 11-year-old children (50.3 % female; 29.6 % overweight/obese), in the Czech Republic, during spring 2012. MVPA was quantified based on the step count (number), MVPA duration, and MVPA heart-rate response (minutes). No differences in the MVPA based on the time during the school day were confirmed in normal-weight versus overweight/obese girls, whereas normal-weight boys significantly exceed their overweight/obese peers in step count and after-school and daylong MVPA. Active participation in PEL contributes to a significantly higher step count, exercise duration, and MVPA heart-rate response in normal-weight and overweight/obese boys (p < 0.001) and normal-weight (p < 0.001) and overweight/obese (p < 0.04) girls during school time. Moreover, active participation in PEL significantly (p < 0.04) increases the overall daily step count, duration, and MVPA heart-rate response in normal-weight boys and overweight/obese girls. Active exercise during PEL accounted for 16.7 % of the total number of steps, 25.1 % of overall MVPA duration, and 24.1 % of the MVPA heart-rate response in 9- to 11-year-old children. During days with a PEL, a significantly (p < 0.02) higher number of overweight/obese girls and a higher number of normal-weight boys achieved the duration of 60 min/day of MVPA compared with days without a PEL. Conclusion: Adding one PEL or an equivalent amount of MVPA to the daily school routine appears to be a promising strategy to effectively increase daily MVPA, particularly among overweight/obese girls.
doi:10.1007/s00431-013-2158-5
PMCID: PMC3930830  PMID: 24061279
Obesity; Physical education; School; Steps; Heart-rate response
19.  EFFECT OF EXCLUSIVE BREASTFEEDING ON THE DEVELOPMENT OF CHILDREN’S COGNITIVE FUNCTION IN THE KRAKOW PROSPECTIVE BIRTH COHORT STUDY 
European journal of pediatrics  2011;171(1):151-158.
The main goal of the study was to assess the effect of exclusive breastfeeding on the neurodevelopment of children over a seven-year follow-up period and to test the hypothesis that the observed cognitive gain in breastfed children in the first years of life is a strong predictor of their cognitive development trajectory, which may be continued in later life.
The analysis is based on data from the seven-year follow-up of 468 term babies (>36 weeks of gestation) born to non-smoking mothers participating in an ongoing prospective cohort study. The cognitive function of children was assessed by psychometric tests performed 5 times at regular intervals from infancy through the preschool age. The study included valid neurodevelopmental assessment of the children – 443 participants were evaluated least twice, 425 – three times and 307 five times in the follow-up period. The association between the cognitive achievements of preschool age children and exclusive breastfeeding of various duration was performed using the GEE (General Estimation Equation) longitudinal model, adjusted for major confounders such as maternal education, gender, parity, and weight gain in pregnancy.
Children breastfed exclusively for up to 3 months had IQs that were on average 2.1 points higher compared to the others (95%CI: 0.24 – 3.9); children breastfed for 4 – 6 months scored higher by 2.6 points (95%CI: 0.87 – 4.27); and the benefit for children breastfed even longer (>6 months) increased by 3.8 points (95%CI: 2.11 – 5.45). Other predictors were maternal education, gender of the child, having an older sibling, and weight gain during pregnancy.
The results of the study support the WHO expert recommendations on exclusive breastfeeding for six months; moreover, they provide evidence that even a shorter duration of exclusive breastfeeding in early infancy produces beneficial effects on the cognitive development of children. The breastfeeding-related IQ gain observed already at the age of 1 was sustained through preschool age and the difference in terms of IQ score between breastfed children and the reference group (mixed breastfeeding) held constant over the whole preschool period.
doi:10.1007/s00431-011-1507-5
PMCID: PMC3747316  PMID: 21660433
breastfeeding; cognitive function in early childhood; prospective birth cohort study
20.  The relationship between selected socioeconomic factors and basic anthropometric parameters of school-aged children and adolescents in Poland 
European Journal of Pediatrics  2013;173(1):45-52.
The aim of the present paper was to examine the associations between anthropometric parameters, overweight, obesity, and socioeconomic status (SES) of children and adolescents in Poland. Data were collected in the “Elaboration of reference blood pressure ranges for children and adolescents in Poland” OLAF-PL0080 (OLAF) study, a nationally representative survey on growth and blood pressure references for children and adolescents aged 7–18 years. Body height, weight, and waist circumference (WC) were measured, and body mass index (BMI) was calculated. Anthropometric parameters were standardized for age and gender and expressed as z-scores. Statistical analyses were conducted on 10,950 children and adolescents whose parents provided socioeconomic questionnaires. The associations between anthropometric parameters, overweight (including obesity), and SES were analyzed using multiple regression and multiple logistic regression. The height was positively associated with higher levels of maternal education and, in the case of girls, also with paternal education. Higher level of income per capita, but not the highest, was associated with higher weight, BMI, and WC and, in the case of boys, also tall stature. The height, weight, BMI, and waist were significantly inversely associated with number of children in the family. Lower number of children in the family and higher level of income, but not the highest, increased odds of overweight and obesity. In the case of girls, the odds of obesity decreased with paternal higher level of education. Conclusion: The social position associated with parents’ education, better environment, and SES correlate with body height and weight of a child. However, it is associated with higher risk of overweight and abdominal obesity.
doi:10.1007/s00431-013-2109-1
PMCID: PMC3890069  PMID: 23918294
Growth; Children; Socioeconomic factors; Overweight; Obesity
21.  Blood parameters changes in cord blood of newborns of hypertensive mothers 
European Journal of Pediatrics  2013;172(11):1501-1509.
The aim of this study was to investigate the changes in the peripheral blood of newborns of hypertensive mothers. The umbilical cord blood from newborns of 31 hypertensive mothers and 32 healthy mothers were examined. In all subjects, complete blood count, peripheral blood smear, reticulocyte count, vitamin B12, folate, ferritin levels and hemoglobin electrophoresis were performed. The subjects were followed up on for 1 year in terms of infections. RBC, hemoglobin, reticulocyte count and normoblast count were higher in the newborns of hypertensive mothers compared to the control group, and total leukocytes, neutrophil, lymphocyte, monocyte, eosinophil, and thrombocyte counts were lower. The number of neutropenic and thrombocytopenic subjects in newborns of hypertensive mothers was higher compared to the control group. On peripheral smears, dysplastic changes in neutrophils and erythrocytes were observed with a higher rate in newborns of hypertensive mothers compared to the control group. HbF levels were found to be higher in newborns of hypertensive mothers compared to the control group. During the follow-up period of 1 year, the number of infections in newborns of hypertensive mothers was found to be higher than the control group. Conclusion: Newborns of hypertensive mothers should be carefully evaluated and monitored in terms of hematologic abnormalities. Complete blood counts and peripheral blood smears can be used as significant parameters for early diagnosis of possible complications.
doi:10.1007/s00431-013-2072-x
PMCID: PMC3825049  PMID: 23812509
Pregnancy; Hypertension; Newborn; Blood parameters
22.  Desmopressin melt improves response and compliance compared with tablet in treatment of primary monosymptomatic nocturnal enuresis 
European Journal of Pediatrics  2013;172(9):1235-1242.
Primary nocturnal enuresis is a prevalent childhood condition that can persist into adulthood. Desmopressin is an antidiuretic available as orally disintegrating lyophilisate (melt) or solid tablet. Recent findings suggesting different food interactions and clinical characteristics, including compliance, between desmopressin melt and tablet motivated a post hoc analysis of a previously reported randomised, crossover study. The efficacy of desmopressin melt compared with tablet was evaluated using the International Children’s Continence Society (ICCS) responder definitions. Compliance was further analysed using detailed criteria, and the association between efficacy and compliance was examined. In total, 221 patients aged 5–15 years, already receiving desmopressin tablets were randomised to the treatment sequence melt (120/240 μg)/tablet (0.2/0.4 mg) or tablet/melt in two consecutive 3-week periods. The probability of being a responder (partial or full) during either period was significantly more likely with desmopressin melt compared with tablet (odds ratio, 2.0; confidence intervals, 1.07–3.73; p = 0.03). There was no period effect on compliance in the tablet/melt sequence and no difference in the number of completely compliant patients in each formulation group; however, more patients were >75 % compliant in period 1 compared with period 2 in the melt/tablet sequence. Increased compliance was associated with greater reductions in the number of wet nights for both formulations. Conclusions: Desmopressin melt, compared with tablet, improves the probability of being a responder. Switching from tablet to melt formulation increased patient compliance. Increased compliance was associated with increased efficacy. Switching to desmopressin melt may benefit patients with suboptimal responses to desmopressin tablet.
doi:10.1007/s00431-013-1992-9
PMCID: PMC3742424  PMID: 23677249
Enuresis; Desmopressin; Compliance; Formulation
23.  The burden of seasonal and pandemic influenza in infants and children 
European Journal of Pediatrics  2013;173(3):265-276.
The burden of influenza is unevenly distributed, with more severe outcomes in children aged <5 years than older children and adults. In spite of this, immunisation policies for young children are far from universal. This article provides an overview of the published evidence on the burden of influenza in children worldwide, with a particular interest in the impact of pandemic influenza in 2009–2010 (caused by the H1N1pdm09 virus). In an average season, up to 9.8 % of 0- to 14-year olds present with influenza, but incidence rates can be markedly higher in younger children. Children aged <5 years have greater rates of hospitalisation and complications than their older counterparts, particularly if the children have co-existing illnesses; historically, this age group have had higher mortality rates from the disease than other children, although during the 2009–2010 pandemic the median age of those who died of influenza was higher than in previous seasons. Admissions to hospital and emergency departments appear to have been more frequent in children with H1N1pdm09 infections than during previous seasonal epidemics, with pneumonia continuing to be a common complication in this setting. Outcomes in children hospitalised with severe disease also seem to have been worse for those infected with H1N1pdm09 viruses compared with seasonal viruses. Studies in children confirm that vaccination reduces the incidence of seasonal influenza and the associated burden, underlining the importance of targeting this group in national immunisation policies. Conclusions: Children aged <5 years are especially vulnerable to influenza, particularly that caused by seasonal viruses, and vaccination in this group can be an effective strategy for reducing disease burden.
doi:10.1007/s00431-013-2023-6
PMCID: PMC3930829  PMID: 23661234
Influenza; Children; Burden; Complication; Hospitalisation; Mortality
24.  Bronchopulmonary dysplasia and neurodevelopmental outcome in extremely preterm neonates 
European Journal of Pediatrics  2013;172(9):1173-1180.
We tested the hypothesis that the use of supplemental oxygen (sO2) at discharge from the NICU in extremely preterm neonates is associated with a greater risk of neurodevelopmental impairment (NDI) at 18 months corrected gestational age (CGA) than the risk of NDI of those neonates discharged in room air. Four hundred twenty-four charts were retrospectively reviewed from infants born at <27 weeks and transferred to Nationwide Children’s Hospital from December 1, 2004 to June 14, 2010. Use of sO2 was evaluated on day of life (dol) 28, at 36 weeks post-menstrual age (PMA), and at discharge. Logistic regression was used to identify postnatal risk factors associated with sO2 at discharge and NDI. At dol 28, 96 % of surviving patients received sO2, and therefore had bronchopulmonary dysplasia (BPD) by definition from a National Institutes of Child Health and Human Development workshop. At 36 weeks PMA, 89 % continued on sO2 (moderate/severe BPD), and at discharge, 74 % continued on sO2. When factors associated with NDI were examined, the need for mechanical ventilation ≥28 days (adjOR = 3.21, p = 0.01), grade III–IV intraventricular hemorrhage (IVH) (adjOR = 4.61, p < 0.01), and discharge at >43 weeks PMA (adjOR = 2.12, p = 0.04) were the strongest predictors of NDI at 18 months CGA. There was no difference in Bayley Scales of Infant Development, third edition composite scores between patients with no/mild BPD and patients with moderate/severe BPD (cognitive p = 0.60, communication p = 0.53, motor p = 0.19) or those scores between patients on and off oxygen at discharge (cognitive p = 0.58, communication p = 0.70, motor p = 0.62). Conclusions: The need for sO2 at discharge is not associated with an increased risk of NDI in these patients. The strongest predictors of poor neurodevelopmental outcome in this population were prolonged positive pressure support, grade III–IV IVH, and discharge at >43 weeks PMA.
doi:10.1007/s00431-013-2016-5
PMCID: PMC3742432  PMID: 23644648
Mechanical ventilation; Supplemental oxygen; Very low birth weight; Intraventricular hemorrhage; Necrotizing enterocolitis
25.  Conductive hearing loss in children with autism 
European Journal of Pediatrics  2013;172(8):1007-1010.
Infantile autism is a serious comprehensive developmental disorder. The diagnosis of hearing loss or its exclusion, which often suggests suspected autism, is very important for early ENT, psychotherapy, and psychiatric treatment. One hundred children diagnosed with autism aged from 3 to 18 years, with a median age of 5 years, were evaluated. The control group of healthy children consisted of 100 children, aged from 3 to 18 years, with a median age of 6 years. Anamnesis and physical examination, including pediatric assessment and otoscopic examination, were carried out on children in both groups. Each child underwent bilateral otoacoustic emission examination in the 0.7, 1, 2, and 4 kHz bands and impedance audiometry examination. The data obtained were subjected to a basic statistical assessment. Chi2 Pearson's test was used to compare results of tests in both groups. The absence of otoacoustic emission for the 1 and 2 kHz bands was significantly more frequent in the group of autistic children than in the control group. Furthermore, types B and C2 tympanometric curves were significantly more common in the group of autistic children than in the group of healthy children.
doi:10.1007/s00431-013-1980-0
PMCID: PMC3722450  PMID: 23474619
Autism; Children; Conductive hearing loss

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