bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of serum low‐density lipoprotein metabolism with oestrogen receptor gene polymorphisms in healthy children
Authors: Kikuchi T , Hashimoto N , Kawasaki T , Uchiyama M
Published: August 2010

The aim of this study was to reveal the association of serum lipid and apolipoprotein levels with oestrogen receptor (ER) Xba I and Pvu II polymorphisms in 102 healthy Japanese school children (56M, 46F) aged 10–15 y. Each genotype of the genomic DNA extracted from peripheral leukocytes was determined using polymerase chain reaction and digestion with Xba I or Pvu II. The genotypes were coded as either X1 or X2 (Xba I) and P1 or P2 (Pvu II), when X1, P1 signified the absence of and X2, P2 the presence of restriction sites. The fasting serum total cholesterol, high‐density lipoprotein cholesterol, low‐density lipoprotein (LDL) cholesterol, triglyceride and apolipoproteins A1, B and E were measured. In the Xba I polymorphism, LDL cholesterol, apolipoprotein B levels of the X1/X1 genotype were significantly higher than those of the others. The other lipid and apolipoprotein levels were not significantly different among the three genotypes. In the Pvu II polymorphism, there were no significant differences in serum lipids and lipoproteins among the three genotypes. This study reveals that Xba I polymorphisms are related to LDL metabolism. These findings support previous reports that the LDL‐lowering effects of oestrogen occur through the ER (α) pathway. The Xba I polymorphism may be one of the genetic factors in the control of LDL metabolism.
Myocardial growth before and after birth: clinical implications*
Authors: Rudolph AM
Published: August 2010

Perinatal changes in myocardial growth have recently evoked considerable interest with regard to cardiac chamber development with congenital cardiac lesions and to myocardial development in preterm infants. It is suggested that cardiac chamber development is influenced by blood flow. Experimental pulmonary stenosis in fetal lambs may induce either greatly reduced or markedly increased right ventricular volume. Ventricular enlargement appears to be associated with a large ventricular volume load resulting from tricuspid valve regurgitation. A small competent tricuspid valve is associated with reduced flow through the ventricle due to outflow obstruction and a small right ventricle. Postnatal growth of the ventricles in congenital heart disease is discussed. Increase in myocardial mass prenatally is achieved by hyperplasia, both during normal development and when myocardial mass is increased by right ventricular outflow obstruction. Postnatally, increases in myocardial mass with normal growth, as well as with ventricular outflow obstruction, are largely due to hypertrophy of myocytes. Myocardial capillary numbers do not increase in proportion with myocyte numbers in ventricular myocardium in association with outflow obstruction. The postnatal effects of these changes in congenital heart lesions are considered. Studies in fetal lambs suggest that the late gestational increase in blood cortisol concentrations is responsible for the change in the pattern of myocardial growth after birth. The concern is raised that prenatal exposure of the premature infant to glucocorticoids, administered to the mother to attempt to prevent hyaline membrane disease in the infant, may inhibit myocyte proliferation and result in a heart with fewer than normal myocytes. This would necessitate that each myocyte would have to hypertrophy abnormally to achieve a normal cardiac mass postnatally.
Epidemic of coeliac disease in Swedish children
Authors: Ivarsson A , Persson LÅ , Nyström L , Ascher H , Cavell B , Danielsson L , Dannaeus A , Lindberg T , Lindquist B , Stenhammar L , Hernell O
Published: August 2010

Coeliac disease has emerged as a public health problem. The aim of the present study was to analyse trends in the occurrence of symptomatic coeliac disease in Swedish children from 1973 to 1997, and to explore any temporal relationship to changes in infant dietary patterns. We established a population‐based prospective incidence register of coeliac disease in 1991, and, in addition, retrospective data from 1973 were collected. A total of 2151 cases fulfilled the diagnostic criteria. Furthermore, we collected national data on a yearly basis on duration of breastfeeding, intake of gluten‐containing cereals and recommendations on when and how to introduce gluten into the diet of infants. From 1985 to 1987 the annual incidence rate in children below 2 y of age increased fourfold to 200‐240 cases per 100 000 person years, followed from 1995 by a sharp decline to the previous level of 50‐60 cases per 100 000 person years. This epidemic pattern is quite unique for a chronic disease of immunological pathogenesis, suggesting that prevention could be possible. The ecological observations made in this study are compatible with the epidemic being the result, at least in part, of a change in and an interplay among three factors within the area of infant feeding, i.e. amount of gluten given, age at introduction of gluten, and whether breastfeeding was ongoing or not when gluten was introduced. Other factor(s) may also have contributed, and the search for these should be intensified.
Pamidronate treatment of bone fibrous dysplasia in nine children with McCune‐Albright syndrome
Authors: Lala R , Matarazzo P , Bertelloni S , Buzi F , Rigon F , de Sanctis C
Published: August 2010

McCune‐Albright syndrome is a rare genetic disorder consisting of skin and bone dysplasia and peripheral endocrinopathies. Little data have been collected regarding bisphosphonate treatment of bone fibrous dysplasia in paediatric patients with this syndrome. The aim of our study was to investigate the therapeutic efficacy of pamidronate in these patients. Nine patients with moderate to severe forms of bone fibrous dysplasia were treated with pamidronate intravenously (0.5‐1 mg/ kg/daily for 2‐3 d) at 0.5‐1‐y intervals. Patients were treated over a time period of 0.5‐3.5 y. During treatment no spontaneous fracture occurred. Bone pain and gait abnormality due to pain disappeared after 2‐3 therapeutic cycles. Cranial asymmetry and limb length discrepancy remained unchanged. Elevated serum alkaline phosphatase and urine hydroxyproline values were reduced by the treatment, demonstrating drug activity at the lesional level. The effectiveness of pamidronate was also seen at the non‐lesional level through an increase in bone density. Radiographic and scintigraphic evidence of lesion healing was not attained. Pamidronate treatment can ameliorate the course of bone fibrous dysplasia in children and adolescents with McCune‐Albright syndrome.
Clinical value of a single postnatal lactate measurement after intrapartum asphyxia
Authors: da Silva S , Hennebert N , Denis R , Wayenberg J‐L
Published: August 2010

Our aim was to compare the respective values of base deficit and lactate in birth asphyxia. Methods: Base deficit and lactate levels were measured from radial artery blood samples taken at 30min of life in 115 term newborns suspected as having been asphyxiated during labour. Both base deficit and lactate levels were compared between patients who further developed moderate or severe encephalopathy and those who experienced no or only mild encephalopathy. Receiver operating characteristics curves and clinical values of both indicators were computed. Results: The correlation between base deficit and lactate was significant (r2= 0.51, p < 0.0001). Both indicators were significantly associated with neonatal outcome. Lactacidaemia lower than 5 mmol/l and/or base deficit level lower than 10 mEq/l were not followed by neurological complications. Plasma lactate concentration greater than 9 mmol/l was associated with moderate or severe encephalopathy with a sensitivity of 84% and a specificity of 67%. Base deficit and lactate had similar clinical values.

Conclusions: Base deficit and lactate measurements in arterial blood at 30 min of life are equally valuable in assessing the severity of birth asphyxia.
Overcoming surfactant inhibition with polymers
Authors: Dargaville PA , Morley CJ
Published: August 2010

Inhibition of the function of pulmonary surfactant in the alveolar space is an important element of the pathophysiology of many lung diseases, including meconium aspiration syndrome, pneumonia and acute respiratory distress syndrome. The known mechanisms by which surfactant dysfunction occurs are (a) competitive inhibition of phospholipid entry into the surface monolayer (e.g. by plasma proteins), and (b) infiltration and destabilization of the surface film by extraneous lipids (e.g. meconium‐derived free fatty acids).

Recent data suggest that addition of non‐ionic polymers such as dextrano and polyethylene glycol to surfactant mixtures may significantly improve resistance to inhibition. Polymers have been found to neutralize the effects of several different inhibitors, and can produce near‐complete restoration of surfactant function. The anti‐inhibitory properties of polymers, and their possible role as an adjunct to surfactant therapy, deserve further exploration.
A review of interventions in the parent‐child relationship informed by attachment theory
Authors: Broberg AG
Published: August 2010

Bowlby's attachment theory has inspired a dramatic shift in the way we understand the development of the early relationship between infant and caregiver(s). Though almost all infants develop an attachment relationship to their primary caregiver(s), not all of them are able to use their caregiver(s) as a secure base or haven of safety from which to explore the world. Mary Ainsworth was the first to describe in detail the aspects of the caregiving system that are most important for the development of the attachment relationship. During the last decade several studies have started to evaluate the possibility that insensitive and perhaps even inadequate parenting can be effectively ameliorated by interventions. The present article sketches the theory behind attachment‐based interventions and reviews the evidence for the effectiveness of such interventions. Finally, the article gives examples of successful preventive as well as therapeutic interventions.
The role of the Swedish Child Health Services in breastfeeding promotion
Authors: Nyqvist K Hedberg , Kylberg E
Published: August 2010

Sweden has one of the highest breastfeeding incidence and duration rates among industrialized countries. Although the Child Health Services offer breastfeeding support to all mothers, there are geographical differences in breastfeeding frequency at different ages. The aims of this study were to describe the present activities in the Child Health Services regarding breastfeeding promotion and to find research evidence regarding interventions. Thirty‐three out of 42 healthcare districts replied to a questionnaire. Differences were found in the transfer of responsibility for newborn infants from hospital to Child Health Centres, criteria for and timing of home visits and recommendations regarding introduction of supplementary food and breastfeeding education for parents and professionals. There were also regional differences in breastfeeding statistics and follow‐up periods.

The following recommendations were made on the basis of the survey and relevant literature: transfer of responsibility for newborn infants must guarantee follow‐up of all mother‐infant pairs; uniform breastfeeding assessment and documentation must be established; all mother‐infant pairs must be offered early home visits, continued on a regular basis by health visitors; drop‐in consultations must be established; a telephone hotline must be set up; for preventive purposes, growth charts must be used based on breastfed infants; evidence‐based guidelines for the introduction of other foods must be followed; information must be provided in parent groups; breastfeeding statistics must use WHO definitions; polyclinics must be available for service to mothers/infants after early discharge and as resources for Child Health Centres; Child and Maternal Health Centres must collaborate; quality assurance programs must be established; breastfeeding courses must be offered in the under‐ and postgraduate training of professionals; compulsory in‐service education must be offered; lactation consultant training must be offered at the university level; and lactation consultant positions must be established.
Weight loss and growth velocity in obese children after very low calorie diet, exercise, and behavior modification
Authors: Sothern MS , Udall JN , Suskind RM , Vargas A , Blecker U
Published: August 2010

The prevalence of obesity in American youth is increasing and treatment of the condition is difficult. We have developed a multi‐disciplinary weight reduction program that extends over 1 y and includes a very low‐calorie diet (VLCD) followed by a hypocaloric diet, exercise, and behavior modification. Based on data collected at baseline, at the end of the acute intervention phase (10–20 wk), and at 1‐y evaluation, we assessed the efficacy of this outpatient weight reduction program in treating obese children and adolescents in a follow‐up of a series of cases. Furthermore, we examined the impact of the approach on growth velocity and maintenance of weight loss at 1 y. Fifty‐six overweight children (aged 7–17 y) were recruited during a period of 18 mo to participate in the weight management program; 52 (93%) completed the acute phase of treatment and 35 (62.5%) successfully completed the I‐y program. There was a significant decrease in body weight and body fat, as assessed by weight determinations and skinfold measurements 0, < 0.0001; results not corrected for age). The body mass index for the 35 individuals who completed the 1‐y program decreased significantly from 32.7 on entry to 28.72 at 1 y (p < 0.0001; results not corrected for age).

Conclusion: We conclude that a multidisciplinary weight reduction program that combines a VLCD, followed by a balanced hypocaloric diet, with a moderate‐intensity progressive exercise program and behavior modification is an effective means for weight reduction in obese children and adolescents.
Prediction of hyperbilirubinaemia in the healthy term newborn
Authors: Carbonell X , Botet F , Figueras J , Riu‐Godó A
Published: August 2010

The aim is to establish the correlation between transcutaneous bilirubin (TCB) and serum bilirubin (TSB) and its predictive value for significant hyperbilirubinaemia ≫290 mcmol/L (17mg/dL). We studied a total of 2004 healthy full‐term newborns, weight 3.230g ± 491g; 90% received breast milk. The study was performed in two phases. In the first phase (610 newborns), the following tests were carried out: hematocrit and bilirubin in umbilical cord blood; TCB at 24 h, 48 h and between 60 h and 96 h at the forehead and over the sternum; TSB was measured along with this last test. In the second phase (1394 newborns), the predictive value of TCB and TSB was validated. The incidence of bilirubin >290 mcmol/L was 2.95% and 3.2%. The correlation between TSB and TCB is high (n= 996; r = 0.92; y = 5.916 + 0.804x; p < 0.000). There was a better correlation between TCB and TSB with sternal compared to forehead determination (< 24 h: 0.81 vs 0.77; 24–48 h: 0.887 vs 0.83; and >48 h: 0.94 vs 0.83). The study showed the scant sensitivity of umbilical cord blood bilirubin and good predictive value at 24 h of TSB > 102 mcmol/L (6mg/dL) and at 48 h of TSB > 154 mcmol/L (9mg/dL) and TCB > 13 (equivalent to 154 mcmol/L).

Conclusion: There is a good correlation between TCB and TSB. In infants with TSB 102 mcmol/L at 24 h or TSB > 154 mcmol/L or transcutaneous readings > 13 h at 48 h, a TSB test must be performed after 48 h of life.
Significance of clinical risk factors of cystic periventricular leukomalacia in infants with different birthweights
Authors: Kubota H , Ohsone Y , Oka F , Sueyoshi T , Takanashi J , Kohno Y
Published: August 2010

Fifteen appropriate‐for‐date premature low‐birthweight infants with cystic periventricular leukomalacia (PVL) were studied. The infants were stratified into three birthweight groups: less than 1000 g, 1000 g and greater but less than 1500 g, and 1500 g or greater. Reported and new risk factors for PVL were compared with control patients for all patients and each birthweight group. Hypocarbia was significantly related to cystic PVL, especially in infants with birthweight 1000 g or greater (p < 0.03). Sensitivity to hypocarbia might be decreased in infants with birthweight less than 1000 g due to therapy or prematurity. In the group with birthweight less than 1000 g, the proportion of cystic PVL infants on continuous intra‐arterial blood‐pressure monitoring tended to be lower than the controls, with an almost significant difference (p= 0.05). The duration of tocolysis was significantly longer in the cystic PVL infants than in the controls when the birthweight was greater than 1500 g (p < 0.04). For some risk factors, a significant difference or a tendency of difference was demonstrated only after stratifying the birthweight. For others, the difference became insignificant after stratification. Assessing risk factors after stratifying by birthweight or degree of prematurity is therefore useful.

Conclusion: The results suggest that hypocarbia should be avoided to prevent cystic PVL, especially in infants with birthweight of 1000 g or greater, continuous intra‐arterial blood‐pressure monitoring may be important in infants with birthweight less than 1000 g, and fetal status should be monitored carefully when the duration of tocolysis is prolonged, especially in infants with birthweight of 1500 g or more.
A randomized double‐blind, placebo‐controlled trial of the EMLA® patch for the reduction of pain associated with intramuscular injection in four to six‐year‐old children
Authors: Cassidy KL , Reid GJ , McGrath PJ , Smith DJ , Brown TL , Finley GA
Published: August 2010

The effectiveness of a eutectic mixture lidocaine‐prilocaine topical anaesthetic cream (EMLA®) patch compared with a placebo patch in the reduction of pain associated with intramuscular immunization was evaluated. As part of the study, 161 children (aged 4‐6‐y) undergoing routine diphtheria, pertussis, tetanus and polio (DPTP) immunization in five urban and five rural private office settings were randomly assigned to an EMLA® patch (n= 83) or a placebo patch control group (n= 78). Pain measurements included: child's self‐report on a Faces Pain Scale; facial action on the Child Facial Coding System; the Children's Hospital of Eastern Ontario Pain Scale and parent and technician ratings on a Visual Analogue Scale. Parents also rated their own and their child's immunization‐related anxiety on a Visual Analogue Scale. The EMLA® patch group had significantly less pain on all four pain measures compared with the placebo group. Of the children in the placebo group, 43% had clinically significant pain, compared with 17% of children in the EMLA® patch group. No severe adverse symptoms occurred as a result of either EMLA® or placebo patch application.

Conclusion: The EMLA® patch reduced immunization pain in 4 to 6‐y‐old children during needle injection.
Urinary excretion of free cysteine in critically ill neonates
Authors: Cambonie G , Bellet H , Houdon L , Vallat C , El Younsi M , Vergnes C
Published: August 2010

In preliminary observations, significant amounts of free cysteine, a neurotoxic amino acid, were noted in the urine of asphyxiated or septic‐shocked neonates. The present study was conducted to determine whether free urinary cysteine was elevated in these critically ill neonates compared with a control group, and to assess the clinical significance of this generation. Free cysteine was measured in the urine of newborn infants with perinatal asphyxia (n= 16) or neonatal sepsis (n= 14) and the urine of a control group (n= 10) by ion‐exchange chromatography. Relationships between cysteine levels and the clinical severity, sulfite supply and neurological outcome of the patients were then studied. Urinary cysteine was 27.6 (15‐49) mmol mol−1creatinine for the patients but was not detectable in the control group. Cysteine levels were correlated with the severity of neonatal septic shock but not with the grade of perinatal asphyxia and did not have a specific influence on the neurological outcome of these patients. The correlation between cysteine level and the severity of neonatal septic shock was indirect and probably linked to higher sulfite administration in this population.

Conclusion: The mean daily supply of sulfites is high in critically ill neonates, mainly originating from dopamine and generating significant amounts of cysteine. Although a worsening effect attributable to cysteine on the neurological outcome of the patients could not be demonstrated, the appropriateness of cryptic administration of sulfites by way of drug excipients is called into question.
A new congenital myopathy in a Norwegian family
Authors: Aurivillius M , Lindal S
Published: August 2010

A 6‐y‐old boy presented with a mild, and apparently non‐progressive, congenital myopathy, primarily affecting explosive movements such as running and jumping. Five other cases, spanning four generations, were identified in his family. A dominant inheritance pattern was suggested. Quadriceps muscle histology showed a selective type II fibre atrophy, which is otherwise considered a non‐specific change associated with a number of conditions.

Conclusion: A Norwegian boy with an inherited muscle weakness is presented. Based on clinical and laboratory investigations, and in light of the inheritance pattern, a previously undescribed congenital myopathy is suggested.
Prediction of bacterial meningitis in children with meningeal signs: reduction of lumbar punctures
Authors: Oostenbrink R , Moons KGM , Donders ART , Grobbee DE , Moll HA
Published: August 2010

Physicians often have to perform a lumbar puncture to ascertain the diagnosis in patients with meningeal signs, because of the serious consequences of missing bacterial meningitis The aim of this study was to derive and validate a clinical rule to predict bacterial meningitis in children with meningeal signs, to guide decisions on the performance of lumbar punctures. Information was collected from records of patients (aged 1 mo to 15 y) consulting the emergency department of the Sophia Children's Hospital between 1988 and 1998 with meningeal signs. Bacterial meningitis was defined as cerebrospinal fluid (CSF) leucocyte count >5 cells μl−1 with a positive bacterial culture of CSF or blood. The diagnostic value of predictors was judged using multivariate logistic modelling and area under the receiver operating characteristic curves (ROC area). In the derivation set (286 patients, years 1988–1995) the duration of the main complaint, vomiting, meningeal irritation, cyanosis, petechiae and disturbed consciousness were independent clinical predictors of bacterial meningitis. The ROC area of this model was 0.92. The only independent predictor from subsequent laboratory tests was the serum C‐reactive protein concentration, increasing the ROC area to 0.95. Without missing a single case, this final model identified 99 patients (35%) without bacterial meningitis. Validation on 74 consecutive patients in 3 subsequent years (1996–1998) yielded similar results.

Conclusion: This prediction rule identifies about 35% of the patients with meningeal signs in whom a lumbar puncture can be withheld without missing a single case of bacterial meningitis. For the individual patient this prediction rule is valuable in deciding whether or not to perform a lumbar puncture.
Activation of the coagulation system occurs within rather than outside cutaneous haemangiomas
Authors: Antovic J , Bakic M , Milicevic R , Gojkovic G , Blombäck M
Published: August 2010

Haemangiomas are the commonest tumours of infancy. They can become even more serious if followed by consumption coagulopathy and even life‐threatening in cases of Kasabach–Merritt syndrome, with thrombocytopenia and haemorrhage. Data exist concerning systemic coagulation abnormalities in children with haemangiomas but to our knowledge there are no data on local consumption coagulopathy in haemangiomaper se.We examined blood coagulation and fibrinolysis parameters in blood withdrawn from haemangioma blood vessels and blood withdrawn from the systemic vein in 14 children with cutaneous haemangiomas (3M, 11F; age range 3 mo to 10 y). Compared with controls, significant decreases in fibrinogen levels, FVII activity, antithrombin and plasmin inhibitor levels and increases in international normalized ratio (INR) and D‐dimer levels were observed in the blood samples withdrawn directly from haemangioma blood vessels. Fibrinogen and antithrombin levels in samples withdrawn from systemic veins were reduced in relation to control values whilst INR values increased, but within normal ranges. D‐dimer levels were increased in peripheral blood. The fibrinogen level was significantly lower and the INR and D‐dimer levels were significantly higher in blood samples from haemangiomas compared to systemic blood. Clinical signs of systemic disseminated intravascular coagulation were not observed.

Conclusions: Our results suggest a strong local activation and local consumption coagulopathy in haemangioma, along with less conspicuous but observable systemic changes in coagulation and fibrinolysis parameters, although without signs of consumptive coagulopathy. These systemic changes could be a reflection of intra‐lesion coagulation activation although there is no evidence to suggest truly systemic disseminated intravascular coagulation.
Antigranulocyte monoclonal antibody immunoscintigraphy in inflammatory bowel disease in children and young adolescents
Authors: Bruno I , Martelossi S , Geatti O , Maggiore G , Guastalla P , Povolato M , Ventura A
Published: August 2010

Aim: Diagnostic delay for inflammatory bowel disease (IBD) is frequent, especially in paediatric patients. Scintigraphy with labelled leucocytes has been proposed as a very sensitive diagnostic tool for detecting bowel inflammation. The aim of this study was to evaluate the sensitivity and specificity of immunoscintigraphy in the diagnosis and follow‐up of children with IBD and to compare this technique with other diagnostic techniques. Methods: Sixty‐six children with histologically confirmed IBD were enrolled in the study. Twenty‐one children in whom IBD was suspected but subsequently not confirmed were used as controls. A total of 138 immunoscintigraphies were performed using 99mTechnetium‐labelled monoclonal anti‐granulocyte antibodies. Immunoscintigraphy was also compared with other diagnostic techniques. Results: Overall sensitivity of monoclonal antibody immunoscintigraphy (MoAb‐IS) in patients with clinically active disease was 94% for Crohn's disease (CD) and 85% for ulcerative colitis (UC). Ultrasonography, endoscopy and radiology were carried out at the same time in 29 patients with CD and in 6 patients with UC: sensitivity of IS was 90% compared with 76% of colonoscopy, 75% for enemas, and 55% for sonography. IS was negative (specificity) in 24% of patients with CD and in 67% of patients with UC during remission, and in 64% of controls with other causes of intestinal inflammation. Diagnostic delay was significantly shorter when compared with a historical cohort of patients.

Conclusion: Immunoscintigraphy is a highly sensitive detector of intestinal inflammation in young patients with IBD and can be useful for reducing diagnostic delay. However, its specificity is low and all positive cases must be confirmed histologically.
Developmental assessment of preterm and term children at 18 months: reproducibility and validity of a postal questionnaire to parents
Authors: Bortolus R , Parazzini F , Trevisanuto D , Cipriani S , Ferrarese P , Zanardo V ,   Gruppo di Studio Metodologie nei Follow‐up Pediatrici
Published: August 2010

Aim: To examine the degree of agreement between the paediatrician's assessment and parental reporting of infants’development using a postal questionnaire. Methods: The developmental status of 241 infants in the charge of 9 community paediatricians or discharged from one Neonatal Intensive Care Unit (NICU) was assessed by their parents 18 mo after delivery, using a postal questionnaire regarding child's height, weight, respiratory, hearing and vision problems, and items taken mainly from the Griffiths’Developmental Scales. At this age, infants were seen by the community or NICU paediatricians, for a complete physical and neurodevelopmental examination. Results: The mean agreement on items regarding developmental areas between parents and paediatricians was 93.0%. In general, parents and professionals agreed on items describing gross motor behaviour (k from 0.39 to 0.83) and disagreed on individual questions describing language/ relational behaviour (k from 0 to 0.38). A 97.9% level of agreement was found for hearing status (k= 0), and 96.2% for assessment of vision (k= 0.29), whereas the level of agreement ranged from 43.2% to 86.2% (k from 0 to 0.15) for the three questions describing respiratory problems. The mean weight and height assessments by paediatricians and parents of infants at 18 mo of age were similar.

Conclusions: Further improvement of the questionnaire is needed, but our findings suggest that this methodology can be considered for use in comparing large cohorts of infants included in randomized clinical trials.
Follow‐up into young adulthood after cardiopulmonary resuscitation in term and near‐term newborn infants. I. Educational achievements and social adjustment
Authors: Kjellmer I , Beijer E , Carlsson G , Hrbek A , Viggedal G
Published: August 2010

Aim: Long‐term sequelae after perinatal asphyxia have generally been assessed at preschool or school age. The aim of the study was to confirm the hypothesis that there could be impairment of cognitive and memory functions that does not become apparent until education and adult life impose special demands. Methods: Seventy‐one term or near‐term newborns in need of cardiopulmonary resuscitation because of presumed perinatal asphyxia were investigated with evoked EEG potentials during the first week of life and were investigated at a follow‐up clinic until 18 mo of age. At that time 12 subjects showed signs of neuro‐developmental impairment. The remaining 59 were considered healthy. They were contacted at young adult age and given a questionnaire containing questions about type of education, need for extra support at school, present activity/employment, living conditions, spare‐time activities and self‐estimation of health. Results: Thirty‐five control subjects were approached at the same time. From the group that was resuscitated at birth, 53 questionnaires were returned and 30 from the control group. Although the resuscitated subjects had signs of both encephalopathy and pathologic evoked responses during their neonatal period, the questionnaire revealed that they had coped with school equally as well as their peers, that the rate of entering university studies was the same and that living conditions were similar between the groups.

Conclusion: These individuals who were resuscitated at birth and who demonstrated various degrees of neonatal encephalopathy suffered either brain injury that could be diagnosed at 18 mo of age or managed as well as their non‐resuscitated peers in terms of educational achievement and social adjustment at young adult age.
Off‐label use of drugs in Italy: a prospective, observational and multicentre study
Authors: Pandolfini C , Impicciatore P , Provasi D , Rocchi F , Campi R , Bonati M ,   Italian Paediatric Off‐label Collaborative Group
Published: August 2010

The aims of the study were to measure the paediatric, off‐label use of drugs in the Italian hospital setting and to reveal areas for priority intervention by investigating the therapeutic indications most involved. Prescriptions given to all children admitted to nine general paediatric hospital wards from December 1998 to February 1999 were analysed. In total, 4265 prescriptions were given to 1461 children, 10 of which were unlicensed and excluded from further analysis. Sixty percent of prescriptions (range between centres: 44‐71%) were off‐label and concerned 89% of children receiving medications (80–96%). The main drug classes were antibacterials, antiasthmatics and analgesics, and represented 56% of off‐label prescriptions. Paracetamol (385 prescriptions) and beclomethasone (339) were the generic substances most often used off‐label. The most common off‐label categories were dosage/frequency (50% of prescriptions), indication and lack of paediatric licence (7% each). Fifty‐four per cent of all indications that led to off‐label prescribing involved only respiratory problems, fever, respiratory tract infections and bronchospasm.

Conclusions: Despite prescription profile differences among centres, off‐label use was high everywhere. Immediate action for more rational drug use is necessary and requires not only regulatory intervention but also a more evidence‐based, therapeutic approach.
Non‐classical 21‐hydroxylase deficiency in children: association of adrenocorticotropic hormone‐stimulated 17‐hydroxyprogesterone with the risk of compound heterozygosity with severe mutations
Authors: Ezquieta B , Cueva E , Varela J , Oliver A , Fernández J , Jariego C
Published: August 2010

Aim: To investigate the association between levels of 17‐hydroxyprogesterone (17‐OHP) and the risk of being compound heterozygous for severe mutations in children with non‐classical 21‐hydroxylase deficiency (NC21OHD). Methods: In 86 Spanish NC21OHD children (75 families) an analysis of the 21‐hydroxylase (21‐OH) gene was performed by CYP21B‐specific polymerase chain reaction amplification, allele‐specific oligonucleotide hybridization and Southern blotting. Familial analysis established how the alleles segregated, and allowed the selection of 21‐OH‐genotyped normal and carrier children, which proved useful in determining a more precise definition of the cut‐off for diagnosis. Receiver operating characteristics (ROC) curve analyses were performed to determine the potential value of 17‐OHP in predicting compound heterozygosity for severe mutations. Results: Thirty‐four of the 86 children (39%) were found to carry one severe 21‐OH mutation (7.3% deletions or conversions, 2.7% 655G, 2.7% Q318X, 1.3% I172N, 1.3% R356W, and 3.3% double microconversions or small conversions involving single exons). The predominant mutation was V281L (56.7%). P453S and P30L were less frequent (3.3 and 2%). No patient showed two severe mutations. The degree of enzymic deficiency, as measured by basal or adrenocorticotropic hormone (ACTH)‐stimulated 17‐OHP levels in fully genotyped patients, but not clinical severity (age and number of symptoms at diagnosis), was found to be significantly greater in children with the severe/mild genotype. ROC curve analyses revealed a strong association between ACTH‐17‐OHP and genotype (area under the curve 0.908, SE 0.057).

Conclusion: ACTH‐stimulated 17‐OHP may predict the risk of severe mutations in compound heterozygosity in children (maximum predictive value 93% sensitivity and 83% specificity for a cut‐off at 151 nmol 1‐1), although a certain overlap in individual values is observed and performance of molecular analysis should never be obviated in the genetic counselling of these patients.
Acute abdominal attack of hereditary angioneurotic oedema associated with ultrasound abnormalities suggestive of acute hepatitis
Authors: Farkas H , Harmat G , Fekete B , Karadi I , Visy B , Varga L
Published: August 2010

Hereditary angioneurotic oedema (HANO) is an autosomal dominant disorder caused by a deficiency of the inhibitor protein C1‐esterase. Recurrent subcutaneous and/or submucosal oedema formation is a hallmark of this disease. HANO is a rare, but potentially life‐threatening disorder with a mortality around 20–30%. Acute oedematous abdominal attacks of HANO can mimic a surgical emergency; this is exemplified by the case of a 14‐y‐old male patient with HANO admitted for such clinical manifestations.

Conclusion: Diagnostic clues include ascites and abnormalities of hepatic structure visible with ultrasound during the oedematous attack. The importance of appropriate treatment is emphasized.
Sexual behaviour and early coitarche in a national sample of 17‐year‐old Swedish boys
Authors: Edgardh K
Published: August 2010

Aim: To describe sexual behaviour as reported by 17‐year‐old boys in Sweden. Methods: The national cross‐sectional SAM 73–90 questionnaire survey was performed in 1990, and comprised 2% of students and school non‐attenders born in 1973. The respondents included 814 students and 92 non‐students, response rates 90.6% and 40.2%, respectively. Data from the two groups are treated separately. Results: In the student group, 54.2% of boys had experienced vaginal intercourse and 16.7% were “early starters” with coitarche before 15 y of age. Independent predictors for coital experience were the vocational study programme OR (odds ratio) 1.91 (95% CI 1.31–2.78), early puberty OR 1.69 (95% CI 1.11–2.57), use of tobacco OR 5.32 (95% CI 2.43–11.7) and alcohol OR 4.09 (2.79–5.98). Sexually transmitted infections (STIs) were reported by 4.1% of coitally active student boys, and impregnating a girlfriend by 4.3%. Of the early starters, 14.6% reported having more than 10 sex partners as compared with 2.5% of the later starters (p > 0.0001) and this was predictive of STI, OR 5.4 (95% CI 1.5–19.7). First‐date intercourse more than twice was predictive of pregnancy, OR 14.4 (95% CI 3.8–54.5). Among school non‐attenders, 74.2% reported coital experience, 33.7% were early starters, and 12.5% had impregnated a girl.

Conclusion: Boys' early sexual experience was related to early puberty, and to general adolescent risk‐taking behaviour. Early coitarche per se was not predictive of STI or pregnancy, but the associated high number of “lifetime” sexual partners and first‐date intercourse were predictive factors. School non‐attenders constituted a group at risk.
Prothrombotic factors in neonates with cerebral thrombosis and intraventricular hemorrhage
Authors: Aronis S , Bouza H , Pergantou H , Kapsimalis Z , Platokouki H , Xanthou M
Published: August 2010

Aim: To investigate whether the factor V Leiden mutation (FVL), the prothrombin gene G20210A variant or the methylenetetrahydrofolate reductase (MTHFR) C677T genotype are risk factors for central nervous system (CNS) thrombosis or intraventricular hemorrhage (IVH) in neonates. Methods: Thirteen full‐term infants with cerebral infarct documented with magnetic resonance imaging were assessed with the whole spectrum of assays for thrombophilia including the three DNA‐based prothrombotic factors. The frequency of congenital defects was compared with that observed in 38 healthy full‐term infants. The genetic defects were also assessed in 55 premature neonates, gestational age <32wk, 17 of whom developed IVH, grade II‐IV. The remaining 38 premature neonates without IVH were used as controls. Results: In the CNS thrombosis group: a prothrombotic factor was detected in 53% of patients and an underlying disease or a triggering event in 61.5%. The frequency of FVL in thrombosed neonates was higher (23%) than in the group of healthy full‐term infants (10.5%), although it did not reach statistical significance. IVH developed in 30.9% of premature neonates. Apart from several maternal or neonatal risk factors for IVH, FII G20210A was found in a considerably higher prevalence in the cohort of neonates with IVH (12%) than in those without (2%), although the difference was not statistically significant.

Conclusion: The pathogenesis of cerebral thrombosis or IVH in neonates is multifactorial. Along with underlying diseases or triggering events, congenital prothrombotic factors (FVL or FII G20210A) showed a trend towards a higher frequency in full‐term infants with CNS thrombosis or premature neonates with IVH than in controls. However, their contribution to neonatal cerebral thrombosis or IVH remains to be determined.
Deficient interferon‐γ receptor‐mediated signaling in neonatal macrophages
Authors: Maródi L
Published: August 2010

Aim: To describe functional and molecular characteristics of interferon‐γ (IFN‐γ) activation in neonatal mononuclear phagocytes (monocytes and macrophages). Methods and Results: Exposure of cord and adult macrophages to IFN‐γ gave quantitatively different results in Candida killing, as well as in release of superoxide anion (O2−). At concentrations of 100 U ml−1 IFN‐γ, maximal increase in these functions with adult macrophages was achieved, whereas no enhancement of killing and O2− release by cord macrophages could be detected. Expression of IFN‐γ receptors was comparable on cord and adult cells and specific binding of [125I]IFN‐γ to cord monocytes and macrophages was even higher compared with adult cells. By flow cytometry, elements of IFN‐γ receptor‐mediated signaling in cord and adult monocytes and macrophages were studied. Monoclonal antibodies against the native form of the signal transducer and activator of transcription‐1 (STAT‐1) revealed comparable expression of this protein in cord and adult macrophages. However, STAT‐1 phosphorylation in response to IFN‐γ was significantly decreased in neonatal monocytes (p < 0.05) and macrophages (p < 0.01) compared with adult cells.

Conclusion: These data suggest deficient cytokine receptor signaling in neonatal mononuclear phagocytes exposed to IFN‐γ.
X‐chromosome inactivation and human genetic disease
Authors: Lyon MF
Published: August 2010

The inactivation of one X‐chromosome in females in early development is the process by which the effective dosage of X‐linked genes is equalized between XX females and XY males. The mechanism that brings this about is the subject of intense research. The X‐linked gene Xist is a key player, which is necessary but not sufficient for the initiation of X‐inactivation. It codes for an untranslated RNA that coats the inactive X‐chromosome, which takes on properties characteristic of heterochromatin, but how this change in chromatin is brought about remains unknown. Because of X‐inactivation, females heterozygous for X‐linked genes are mixtures of two types of cells and show a variable phenotype. The proportion s of the two types of cells can depart from equality due to cell selection either at the tissue or whole organism level. In rare cases, changes in the Xist gene can cause skewing of X‐inactivation. A few genes escape from X‐inactivation either wholly or partially.

Conclusion: X‐chromosome inactivation is a physiological mechanism that equalizes gene‐dosage effects on the sex chromosomes. The occurrence of this normal process affects the phenotype seen in females carrying X‐linked mutant genes or chromosome anomalies.
Preschool children with developmental coordination disorder: a short‐term follow‐up of motor status at seven to eight years of age
Authors: Pless M , Carlsson M , Sundelin C , Persson K
Published: August 2010

At a population‐based screening of 5–6‐y‐old children, 37 children were identified as having definite or borderline motor difficulties consistent with developmental coordination disorder. When 7–8 y old they were re‐examined to determine their current motor status and to compare it with that at the age of 5–6 y. The motor status was investigated from three perspectives: by a motor test, by the use of a self‐perceived motor competence scale, and from the parents' descriptions. On a group level the children had not changed their motor status when 7–8 y old, according to the total scores in the Movement ABC motor test and the Perceived Motor Competence scale. On an individual level most children with definite motor difficulties remained in their category regarding motor difficulties at the follow‐up, while most children with borderline motor difficulties did not. The parents' descriptions indicated an association between willingness to engage in physical activities and degree of motor difficulties.

Conclusion: Over a period of 1.5 y most children with definite motor difficulties continued to have such difficulties. The parents' descriptions of their children's motor status and development were in agreement with the children's motor status as measured by a motor test, but were not in total accordance with the children's self‐perceived competence.
Vaccination coverage estimates by EPI cluster sampling survey of children (18–24 months) in Flanders, Belgium
Authors: Vellinga A , Depoorter AM , Van Damme P
Published: August 2010

A random cluster sample according to the EPI cluster sampling technique was conducted in 1999 in Flanders (North Belgium) to ascertain the vaccination coverage of 18 to 24‐mo‐old children. Polio is the only mandatory vaccine. Diphtheria‐tetanus‐pertussis (DTP), Haemophilus influenzae type b (Hib), hepatitis B (HB) and measles‐mumps‐rubella (MMR) are included in the recommended schedule of vaccinations. For Hib and HB, a minimal cost was charged. Professional interviewers conducted interviews with the parents of 1110 children randomly selected in 89 municipalities. Analysis was conducted on the results of 1005 children. The coverage level (95% confidence interval) for the full schedule was 96% (95–97) for polio, 89% (87–91) for DTP, 78% (74–82) for Hib, 68% (64–72) for HB and 83% (81–87) for MMR. The vaccinations were administered by the regional children's health organization (70%), paediatricians (17%) and GPs (11%). No sociodemographic factors could be associated with vaccination coverage. One province showed significantly (p >0.01) lower vaccination coverage levels compared with those of the other four provinces for DTP (91% vs 82%), Hib (78% vs 53%), HB (73% vs 46%) and MMR (87% vs 66%).

Conclusion: There is a need for more and better information about vaccination for parents as well as for the healthcare providers.
Lung function and asthma symptoms in children: relationships and response to treatment
Authors: Mitra AD , Ogston S , Crighton A , Mukhopadhyay S
Published: August 2010

The aim of this study was to determine the relationships between the forced expiratory volume in 1 s (FEV1), peak expiratory flow (PEF) and asthma symptom scores, as well as their response to treatment, in children with no recent exacerbations of asthma. Asthma symptom scores, FEV1 and PEF were characterised, and their relationships and changes at follow‐up studied in 64 children (mean age 9.5 y) referred to asthma outpatients. The mean FEV1 and PEF at the initial clinic visit were 94% of predicted values. At follow‐up, mean FEV1 and PEF were similar. However, symptom scores (maximum obtainable score for each variable = 3) for exercise, nocturnal cough and morning cough were abnormal at the initial visit (mean ± SD, exercise 1.0 ± 0.7, nocturnal cough 1.7 ± 1.2, morning cough 1.6 ± 1.2) and improved significantly at follow‐up (exercise 0.8 ± 0.7, nocturnal cough 0.9 ± 1.1, morning cough 1.0 ± 1.2) (p > 0.05). A significant relationship was not observed between lung function and total symptom score, at either the initial or follow‐up clinic visit. Neither FEV1 nor PEF significantly correlated with individual symptom scores. While symptom control improved, no significant relationships between change in asthma symptom scores and change in FEV1 and PEF between the initial and follow‐up visits were observed.

Conclusion: Clinic (“office”) spirometry, currently performed world‐wide, cannot be uniformly regarded as an indicator of asthma status. In addition to the measurement of lung function, quantitative symptom scoring may be a helpful tool for physicians in the assessment of childhood asthma status.