bluuebunny/crossref_metadata_2025 huggingface dataset:
Breastfeeding, very long polyunsaturated fatty acids (PUFA) and IQ at 6/4 years of age
Authors: Gustafsson PA , Duchén K , Birberg U , Karlsson T
Published: August 2010

Aim: Breastfeeding seems to be favorable for cognitive development. Could levels of polyunsaturated fatty acids (PUFA) explain this?Methods: Pregnant mothers were recruited consecutively at maternity care centres. PUFA were analysed in colostrum and breast milk at 1 and 3 mo. The product‐precursor ratios of n‐6+n‐3 PUFA were examined as measures of activity in respective steps in the fatty acid metabolic chain. Also, the quotient between DHA and AA was analysed. The children were tested with the full WISC‐III at 6.5 y. Results: First, the influence of length of breastfeeding was analysed by multiple regression together with relevant cofactors (except for PUFA). In the best models, 46% of the variation in total IQ was explained. Length of breastfeeding contributed significantly to total IQ (beta = 0.228, p= 0.021), verbal IQ (beta = 0.204, p= 0.040) and performance IQ (beta = 0.210, p= 0.056). There were no significant single correlations between PUFA and measures of cognitive development. However, in multiple regression analysis of colostrum, significant beta‐coefficients were found for steps 4+5 in the fatty acid metabolic chain (beta = 0.559, p= 0.002). If length of breastfeeding and gestation week were added to steps 4+5, this three‐factor model could explain 67% of the variation of total IQ. Introducing length of breastfeeding and gestation week together with the quotient DHA/AA (beta = 0.510, p > 0.001) yielded a three‐factor model, which explained 76% of the variation in total IQ.

Conclusion: Our findings could be interpreted as supporting the importance of high levels of PUFA for cognitive development. However, the sample is small and the results must be interpreted with caution.
Pulmonary outcome in adolescents of extreme preterm birth: a regional cohort study
Authors: Halvorsen T , Skadberg BT , Eide GE , Røksund O Drange , Carlsen KH , Bakke P
Published: August 2010

Aims: The pulmonary outcome of extreme prematurity remains to be established in adults. We determined respiratory health and lung function status in a population‐based, complete cohort of young preterms approaching adulthood. Methods. Forty‐six preterms with gestational age ±28 wk or birthweight ±1000g, born between 1982 and 1985, were compared to the temporally nearest term‐born subject of equal gender. Spirometry, plethysmography, reversibility test to salbutamol and methacholine bronchial provocation test were performed. Neonatal data were obtained from hospital records and current symptoms from validated questionnaires. Results: When entering the study at a mean age of 17.7 (SD: 1.2) y, a doctor's diagnosis of asthma and use of asthma inhalers were significantly more prevalent among preterms than controls (one asthmatic control compared to nine preterms, all but one using asthma inhalers). Peak expiratory flow (PEF) and forced expiratory volume in 1 s (FEV1) were decreased and the discrepancies relative to controls increased parallel to increased severity of neonatal lung disease. Parameters of increased neonatal oxygen exposure significantly predicted FEV1. Adjusted for height, gender and age, FEV1 was reduced by a mean of 580 ml/s in subjects with a history of bronchopulmonary dysplasia. Fifty‐six percent of preterms had a positive methacholine provocation test compared to 26% of controls.

Conclusion: A substantially decreased FEV1, increased bronchial hyperresponsiveness and a number of established risk factors for steeper age‐related decline in lung function were observed in preterms. A potential for early onset chronic obstructive pulmonary disease is present in subsets of this group.
Birthweight of full‐term infants is associated with cord blood CD34+ cell concentration
Authors: Aroviita P , Teramo K , Hiilesmaa V , Westman P , Kekomäki R
Published: August 2010

Aim: CD34+ cell counts are used to define the haematopoietic stem cell potential of a given cord blood transplant. The aim was to test the hypothesis that high concentration of cord blood haematopoietic progenitor and stem cells could be a reflection of intrauterine growth, of which birthweight is an indicator. Methods: Simple and multiple regression analyses were applied to test cord blood bank data on 1368 infants for associations of selected obstetric factors and cellular contents of cord blood. Results: When groups were formed based on the extreme values (5th versus 95th percentiles) of a given variable, e.g. birthweight, the term infants having the highest birthweights were found to have statistically significantly higher median cord blood CD34+ cell concentrations. Also, infants in the top 50th percentile of relative birthweight had higher median CD34+ cell concentration than infants in the low 50th percentile. In multiple regression analysis, the correlation between birthweight and CD34+ cell concentration was statistically clearly significant. Notably, while an expected correlation between gestational age and nucleated cell concentration was found, there was no association between infant gestational age and CD34+ cell concentration.

Conclusion: Haematopoietic progenitor and stem cells may reflect intrauterine growth and have a more central role in foetal development than has been reported earlier.
Re‐hospitalization in infants younger than 29 weeks’ gestation in the EPIPAGE cohort
Authors: Lamarche‐Vadel A , Blondel B , Truffert P , Burguet A , Cambonie G , Selton D , Arnaud C , Lardennois C , du Mazaubrun C , N'Guyen S , Mathis J , Bréart G , Kaminski M ,   The EPIPAGE Study Group
Published: August 2010

Aim: To estimate the re‐hospitalization rate of extremely preterm children during infancy and associated factors after the recent improvement in survival rates. Method: The cohort included all children born before 29 wk of gestation in nine French regions in 1997. All admissions between discharge from initial hospitalization and 9 mo after birth were considered. Factors studied included the child's characteristics at birth and during neonatal hospitalization, risk factors for infection after discharge and parents' socio‐demographic characteristics. Adjusted odds ratios (aOR) for re‐hospitalization for all reasons and for respiratory disorders were obtained from logistic regression models. Results: Of the 376 children, 178 were re‐admitted at least once (47.3%; 95% CI: 42.3–52.4). Fifty‐five percent of the hospitalized children were admitted at least once for respiratory disorders. The re‐hospitalization rate was higher for children who had had chronic lung disease (aOR: 2.2; 95% CI: 1.3–3.7), those initially discharged between August and October (aOR: 2.5; 95% CI: 1.2–5.1) or between November and January (aOR: 3.2; 95% CI: 1.5–6.8), and children living with other children under six (aOR: 3.4; 95 %CI: 1.6–7.5). Re‐hospitalizations were associated with neither gestational age nor the duration of neonatal hospitalization. Adjusted odds ratios for re‐hospitalization for respiratory tract disorders were very similar to those for the overall hospitalizations.

Conclusion: Infants born before 29 wk have a very high risk of re‐hospitalization. The associated factors can help define high‐risk groups at discharge from the neonatal unit who need special surveillance.
Maternal predictors of subcutaneous fat in the term newborn
Authors: Guihard‐Costa A‐M , Papiernik E , Kolb S
Published: August 2010

Aim: To determine the relative influences of some maternal factors on skinfold thickness. The effects of age, parity, height, body mass index (BMI) and pregnancy weight gain (PWG) of the mother on the subscapular skinfold thickness (SST) of the newborn were estimated, and compared with their effects on birthweight (BW), crown‐heel length (CHL) and head circumference (HC). Methods: A sample of 13, 972 healthy, term singletons was selected at the Clamart Maternity Hospital (France). Stepwise regressions were used to determine the most predictive maternal factors for each parameter in the newborn. The respective effects of the mother's age and parity on each newborn dimension were tested by analysis of variance. Results: The SST is a singular parameter, influenced by the mother's BMI and PWG, but not by her height. In contrast, the main predictor of BW, CHL and HC is the height of the mother, and to a lesser extent her PWG and BMI. Parity and maternal age have a smaller effect, except on SST, and essentially between the first and second pregnancies.

Conclusion: These results clearly separate SST from other newborn dimensions. The skinfold thickness depends only on the nutritional status of the mother, while other dimensions are markedly influenced by the genetic background. This study is the first to demonstrate the singularity of skinfold thickness in newborn infants as a marker of the mother's nutritional status.
Barth syndrome without 3‐methylglutaconic aciduria
Authors: Schmidt M Rahbek , Birkebaek N , Gonzalez I , Sunde L
Published: August 2010

Barth syndrome involves cardiomyopathy, skeletal myopathy, neutropenia and 3‐methylglutaconic (3‐mgc) aciduria. 3‐mgc aciduria has been observed in almost all reported cases and has served as a diagnostic criterion.

Conclusion: A case of confirmed BTHS, but without 3‐mgc aciduria, emphasizes the importance of extensive investigations in cases with suspected hereditary cardiomyopathy.
Randomized controlled trial of skin‐to‐skin contact from birth versus conventional incubator for physiological stabilization in 1200‐ to 2199‐gram newborns
Authors: Bergman NJ , Linley LL , Fawcus SR
Published: August 2010

Aim: Conventional care of prematurely born infants involves extended maternal‐infant separation and incubator care. Recent research has shown that separation causes adverse effects. Maternal‐infant skin‐to‐skin contact (SSC) provides an alternative habitat to the incubator, with proven benefits for stable prematures; this has not been established for unstable or newborn low‐birthweight infants. SSC from birth was therefore compared to incubator care for infants between 1200 and 2199 g at birth. Methods: This was a prospective, unblinded, randomized controlled clinical trial; potential subjects were identified before delivery and randomized by computerized minimization technique at 5 min if eligible. Standardized care and observations were maintained for 6 h. Stability was measured in terms of a set of pre‐determined physiological parameters, and a composite cardio‐respiratory stabilization score (SCRIP). Results: 34 infants were analysed in comparable groups: 3/18 SSC compared to 12/13 incubator babies exceeded the pre‐determined parameters (p < 0.001). Stabilization scores were 77.11 for SSC versus 74.23 for incubator (maximum 78), mean difference 2.88 (95% CI: 0.3–5.46, p = 0.031). All 18 SSC subjects were stable in the sixth hour, compared to 6/13 incubator infants. Eight out of 13 incubator subjects experienced hypothermia.

Conclusion: Newborn care provided by skin‐to‐skin contact on the mother's chest results in better physiological outcomes and stability than the same care provided in closed servo‐controlled incubators. The cardio‐respiratory instability seen in separated infants in the first 6 h is consistent with mammalian “protest‐despair” biology, and with “hyper‐arousal and dissociation” response patterns described in human infants: newborns should not be separated from their mothers.
Methicillin‐resistantStaphylococcus aureusbacteraemia in neonatal intensive care units: an analysis of 90 episodes
Authors: Chuang Y‐Y , Huang Y‐C , Lee C‐Y , Lin T‐Y , Lien R , Chou Y‐H
Published: August 2010

Aim: To delineate the clinical features of methicillin‐resistantStaphylococcus aureus(MRSA) bacteraemia in infants hospitalized at the neonatal intensive care unit.Methods: Episodes of MRSA bacteraemia in Chang Gung Children's Hospital neonatal intensive care unit from 1997 to 1999 were reviewed for incidence, predisposing factors, clinical presentations, treatment and outcome.Results: Ninety episodes of MRSA bacteraemia were identified. The overall rate of MRSA bacteraemia was 1.05 per 1000 patient days during the 3‐y period. Most of the patients were premature infants (76%), with prior operation or invasive procedures (39%), had an indwelling intravascular catheter (79%) and exposure to antibiotic therapy (96%). A localized cutaneous infection was found in 53.3% of the episodes. The most common clinical diagnoses were catheter‐related infections (54.4%), skin and soft tissue infections (21.1%), bacteraemia without a focus (20%) and pneumonia (16.7%). Metastatic infection occurred in 18% of these infants. Among the patients treated with vancomycin for ±14d, 88.7% did not develop any complications, and 11.3% developed a recurrence.

Conclusions: MRSA is an established pathogen in our NICU. MRSA bacteraemia in the neonates predominantly presented as catheter‐related infections, and metastatic infections were not infrequently seen. In uncomplicated MRSA bacteraemia, treatment with vancomycin for ±14 d seems to be adequate.
Relationship of maternal autoimmune response to clinical manifestations in children with congenital complete heart block
Authors: Eronen M , Miettinen A , Walle TK , Chan EKL , Julkunen H
Published: August 2010

Objective: To study the autoimmune response in mothers of children with congenital heart block (CHB) diagnosed at different ages and with different clinical manifestations. Patients and methods: Clinical data and sera for the determination of immunological tests were available from 104 mothers of 113 children born between 1950 and 2000 and diagnosed with CHB before the age of 16 y. Prenatal diagnosis was performed in 74 (65%) children of 65 mothers, and 39 (35%) children had postnatal diagnosis of CHB. Maternal antibodies to 52 kd and 60 kd SS‐A, and to 48 kd SS‐B were determined by time‐resolved fluoroimmunoassay (TR‐FIA) and to antinuclear antibodies (ANA) by immunoflurescense (IF). Results: Out of the 65 mothers of children with in utero diagnosed CHB, 88% had antibodies to 52 kd SS‐A and 83% had ANA. Antibodies to 60 kd SS‐A and 48 kd SS‐B were less frequently present, in 48% and in 54% of the mothers, respectively. Seven (11 %) of the mothers were negative by all immunoassays. Of the 13 mothers of children with in‐infancy diagnosed CHB, one mother had high‐titer ANA. After 1 y of age, CHB was diagnosed in 26 children; at 1 to 6 y in 16 and after 7 y in 10 children; 1/16 and 1/10 patients had positive antibodies. In all twin pregnancies (n= 4) and in all families with recurring cases of CHB (n= 5), maternal antibodies were positive in at least one assay. The titer of 48 kd anti‐SS‐B antibodies was significantly higher in children with cutaneous neonatal lupus (98.1 vs 41.0; p= 0.02). All mothers whose children died before the age of 4 y (n= 8) and 85 % (11/13) of mothers whose children developed cardiomyopathy had elevated antibody titers in at least one assay. However, we could not find any prognostic value of maternal antibody levels or specificities on the clinical outcome of the children with CHB.

Conclusions: Although rare, late detection or postnatal progression of CHB in antibody‐mediated CHB should be taken into consideration. Maternal antibody levels or specificities have prognostic effect neither on the clinical outcome of the child with CHB nor on the risk of reappearance in the same family.
Prevalence and significance of minor anomalies in children with impaired development
Authors: Ulovec Z , Šoši± Z , Škrinjari± I , ±atovi± A , Čivljak M , Szirovicza L
Published: August 2010

Aim: To compare the prevalence of Waldrop's minor physical anomalies in children with developmental disorders (mental retardation, hearing and visual impairment) and healthy schoolchildren. Methods: The study was carried out on a sample of 469 children (223 children with developmental disorders and 246 healthy schoolchildren). Results: Significant differences were found between the children with developmental disorders and the healthy children with regard to the number of minor anomalies and their weighted scores according to Waldrop. Multivariate discriminant analysis with two discriminative functions explained as much as 96.51% of the total variability and significantly distinguished the healthy children from the children with developmental disorders. However, no clear distinction was found between the mentally retarded children and those with visual impairment. Interrelation of the number and sum of the weighted scores of minor anomalies showed similar minor anomalies in the mentally retarded children (mean per person 3.65 and 3.82, respectively), the children with visual impairment (3.24 and 3.50), the children with hearing impairment (3.84 and 3.67) and the control group (1.70 and 1.46), although at different levels.

Conclusions: The high prevalence of multiple minor anomalies in children with developmental disorders suggests that during early development, factors which cause the specific developmental disorder and the occurrence of a minor anomaly have a joint effect.
Control of β‐catenin/Tcf‐directed transcription in medulloblastoma
Authors: Raffel C
Published: August 2010

The β‐catenin, glycogen synthase kinase 3β (GSK‐3β), and adenomatous polyposis coli (APC) gene products interact to form a network that influences the rate of cell proliferation. Medulloblastoma occurs as part of Turcot's syndrome and patients with Turcot's syndrome, who develop medulloblastomas, have been shown to harbor germline APC mutations. While APC mutations have been investigated and not identified in sporadic medulloblastomas, the status of the β‐catenin and GSK‐3β genes has not been evaluated in this tumor. This study shows that 3 of 67 medulloblastomas harbor β‐catenin mutations, each of which converts a GSK‐3β phosphorylation site from serine to cysteine. The β‐catenin mutation seen in the tumors was not present in matched constitutional DNA in the 2 cases where matched normal DNA was available. A loss of heterozygosity (LOH) analysis of 32 medulloblastomas with paired normal DNA samples was performed with 4 microsatellite markers flanking the GSK‐3β locus; LOH with at least one marker was identified in 7 tumors. Sequencing of the remaining GSK‐3β allele in these cases failed to identify any mutations. Taken together, these data suggest that activating mutations in the β‐catenin gene may be involved in the development of a subset of medulloblastomas. The GSK‐3β gene does not appear to be a target for inactivation in this tumor.
Clinical biochemical genetics in the twenty‐first century
Authors: Rinaldo P , Hahn S , Matern D
Published: August 2010

Genetic disorders are recognized to play an increasing role in pediatrics. Close to 10% of diseases among hospitalized children have been ascribed to Mendelian traits inherited as single gene defects, not a surprising figure considering that approximately 1000 inborn errors of metabolism (IEM) have been identified to date, primarily through the detection of endogenous metabolites abnormally accumulated in biological fluids and tissues. The laboratory discipline that covers the biochemical diagnosis of IEM is known as clinical biochemical genetics, and is defined as one concerned with the evaluation and diagnosis of patients and families with inherited metabolic disease, monitoring of treatment, and distinguishing heterozygous carriers from non‐carriers by metabolite and enzymic analysis of physiological fluids and tissues. The biochemical genetics laboratory differs from the clinical chemistry laboratory in the extent of interpretation necessary to make its results meaningful to the clinician. While dramatic advances in molecular genetics have greatly changed the landscape of diagnostic options for many genetic disorders, a biochemical approach remains the dominant force for the diagnosis and monitoring of IEM. Owing to the stereotypical clinical presentation of many of these disorders, a major role of the biochemical genetics laboratory is to analyze ever more complex metabolic profiles to reach a preliminary diagnosis, which then needs to be confirmed by enzymic and/or molecular studies in vitro. Accordingly, the role of biochemical genetics in the pediatric practice of the 21st century is to provide a multicomponent screening process that can be divided into four major components: (i) at‐risk screening (prenatal diagnosis); (ii) newborn screening (testing of presymptomatic patients); (iii) high‐risk screening (testing of symptomatic patients); and (iv) postmortem screening (metabolic autopsy). The focus of our laboratory is to apply state‐of‐the‐art technology such as tandem mass spectrometry to bring as many as possible IEM within the boundaries of newborn screening programs, and to investigate the role played by individual disorders in maternal complications of pregnancy, pediatric acute/fulminant liver failure, and sudden and unexpected death in early life.
How much glutamate is toxic in paediatric parenteral nutrition?
Authors: Hermanussen M. , Tresguerres J. A. F.
Published: August 2010

Aim: To discuss a hypothesis regarding the impact and possible side effects of glutamate in paediatric parenteral nutrition. Results: Published evidence suggests that the arcuate nucleus, which is a potent site of leptin action, is severely damaged by elevated glutamate levels. Early administration of glutamate (GLU) to the neonatal rat disrupts the hypothalamic signalling cascade of leptin action.

Conclusion: We are concerned that GLU‐containing parenteral nutrition may not only increase the risk of hypothalamic damage in neurosurgical patients with an impaired blood–brain barrier, and in patients with periventricular leukomalacia, but may also permanently damage the arcuate nucleus neurones in the very immature infant. This may result in later impairment of feeding regulation, obesity, hyperleptinaemia, and other symptoms that characterize the “thrifty phenotype” and the dysmetabolic syndrome. We strongly suggest reconsidering the recommended daily allowances of amino acids, particularly the use of GLU, in current paediatric parenteral nutrition.
Carotid artery intima‐media thickness and angiotensin‐converting enzyme gene polymorphism in the offspring of parents with premature stroke
Authors: Marčun Varda N. , Peterlin B. , Bradač S. Umek , Gregorič A.
Published: August 2010

Aim: To determine some common cardiovascular risk factors, alterations in the measurements of intima‐media thickness (IMT) and the distribution of the angiotensin‐converting enzyme (ACE) polymorphism in children of parents with premature stroke, and to investigate the cardiovascular risk of these children and the potential need for some preventive measures.Methods: A family history of cardiovascular disease represents a cardiovascular risk factor in the offspring. This association has not yet been clearly determined for cerebrovascular accidents. New technology allows us to investigate the risk for cardiovascular disease at an early presymptomatic stage. We applied the measurement of IMT of carotid arteries by ultrasound imaging and the determination of the ACE insertion/deletion (I/D) polymorphism in blood to evaluate the predisposition for cerebrovascular disease in the offspring of patients with previous stroke. We investigated 58 subjects whose parents had experienced a cerebrovascular accident before the age of 45 y and compared them with a matched control group whose parents had not suffered a stroke. Results: The results of IMT at various sites of the carotid arteries and the genotype distribution of the ACE gene were not significantly different between the study group and the control group. In addition, no differences were found in the serum levels of lipid fractions or other biochemical variables.

Conclusion: We conclude that determination of the carotid IMT and of the ACE I/D polymorphism do not permit discrimination of the cardiovascular risk in children of parents with or without premature stroke.
Development and validation of the ABC pain scale for healthy full‐term babies
Authors: Bellieni Carlo V , Bagnoli Franco , Sisto Renata , Neri Laura , Cordelli Duccio , Buonocore Giuseppe
Published: August 2010

Aim: We developed and validated a pain scale (ABC scale) for term babies based on acoustic features of crying. Methods: The scale consisted of three different cry parameters: (a) pitch of the first cry; (b) rhythmicity of the crying bout; (c) constancy of crying intensity. These parameters were previously found to distinguish between medium and high levels of pain measured by spectral analysis of crying. We validated the scale using healthy term babies undergoing routine heel prick. Concurrent validity was assessed comparing pain values obtained with our scale with those obtained with another pain scale; this relationship was also used to assess the sensitivity of the scale. To assess specificity we compared the ABC scores during a painful event (heel prick) with two non‐painful events (preliminary phase of prick in the same group of babies, and heel prick with analgesia in another group). Results: Specificity: (a) analgesic/non‐analgesic comparison, p<0.0001; (b) pain/sham comparison, p<0.0001). Sensitivity: a high correlation between scores of the ABC scale and the Douleur Aigue du Nouveau‐Né scale indicates good sensitivity. Concurrent validity: Spearman ρ=0.91. Internal consistency: Cronbach's α=0.76. Inter‐rater reliability: Cohen's κ for multiple raters=0.83. Intra‐rater reliability: Cohen's κ=0.85. Practicality: All nurses who used it scored the scale as “good”.

Conclusion: The ABC scale proved to be simple and reliable for assessing pain in healthy, non‐intubated term newborns.
Discitis in toddlers: A case series and review
Authors: Karabouta Zacharoula , Bisbinas Ilias , Davidson Anne , Goldsworthy Lisa L
Published: August 2010

Toddlers commonly present to medical services with non‐specific symptoms. The presence of refusal to walk and nocturnal waking with crying should alert clinicians to the possibility of discitis.

Conclusion: Features that may alert clinicians to the diagnosis of discitis in young children are reviewed.
Effect of regular ingestion of Saccharomyces boulardii plus inulin or Lactobacillus acidophilus LB in children colonized by Helicobacter pylori
Authors: Gotteland Martin , Poliak Laura , Cruchet Sylvia , Brunser Oscar
Published: August 2010

Aim: To evaluate the effect of a probiotic, Lactobacillus acidophilus LB (LB), or a synbiotic, Saccharomyces boulardii plus inulin (SbI), on Helicobacter pylori (Hp) colonization in children. Subjects and methods: A clinical trial was carried out in a school from a low socio‐economic area of Santiago. Two hundred and fifty‐four asymptomatic children (8.40±1.62 y) were screened for Hp by the 13C‐Urea Breath Test (13C‐UBT). Hp‐positive children were randomly distributed into three groups to receive either antibiotic treatment (lanzoprazole, clarythromycin and amoxicillin) for 8 d, or SbI or LB daily for 8 wk. A second 13C‐UBT was carried out at this time. Spontaneous clearance was evaluated in the same way in 81 infected, untreated children. The differences in the δ13CO2 over baseline values before and after treatments (ΔDOB) were evaluated. Results: 182 subjects (71.7%) were colonized by Hp, and 141 of them completed their treatment (22.5% dropout). Hp was eradicated in 66%, 12% and 6.5% of the children from the Ab, SbI and LB groups, respectively, while no spontaneous clearance was observed in the children without treatment. A moderate but significant difference in ΔDOB was detected in children receiving living SbI (−6.31; 95% CI: −11.84 to −0.79), but not in those receiving LB (+0.70; 95% CI: −5.84 to +7.24).

Conclusion:
S. boulardii seems promising as an agent that interferes with Hp in colonized individuals. More studies are needed to confirm these results and to elucidate the mechanisms by which Sb inhibits Hp.
Prescribers' indications for drugs in childhood: A survey of five European countries (Spain, France, Bulgaria, Slovakia and Russia)
Authors: Sanz Emilio J , Hernández Miguel A , Ratchina Svetla , Stratchounsky Leonid , Asuncion Peiré Maria , Lapeyre Mestre Maryse , Horen Bernard , Kriska Milan , Krajnakova Halina , Momcheva Hristina , Encheva Daniela , Martínez‐mir Inocencia , Palop Vicente
Published: August 2010

Background: Indication‐based, in comparison to diagnoses‐based, drug utilization studies in children are scarce in the literature. Aim: To determine the adequacy of the prescriber's indications for specific drug treatments compared to the current literature in five different European countries; and to show the possibilities of performing indication‐based drug utilization studies. Design: a descriptive, cross‐sectional, international study. Patients and methods: Randomly selected sample of 12 264 paediatric outpatients seen in consultation rooms attended by paediatricians or general practitioners. Data on patient demographics, diagnoses, and pharmacological treatment, with therapeutic indications for each drug, were collected in pre‐designed forms. Diagnoses and indications were coded using the ICD‐9 and drugs according to the ATC classifications. Results: Indications were registered for every drug prescribed in all locations. Antibiotic indications considered incorrect (common cold, upper respiratory tract infections, viral infections, general symptoms or “not specified”) accounted from 24.1% of the total antibiotics prescribed in Tenerife to 67.4% in Slovakia. Incorrect indication of first‐choice antibiotics prescribed in acute otitis media and tonsillitis ranged from 28.9% of total antibiotics use in Russia to 75.4% in Tenerife. Correct antibiotic indications ranged from 23.4% of total antibiotics used in Slovakia to 65.7% in Tenerife. Aspirin use in febrile viral conditions was detected mainly in Toulouse and Russia.

Conclusion: The main areas for improvement detected were high use of mucolytics, prescription of aspirin in potential or established viral infections, overuse of antibiotics and identification of specific patterns of incorrect antibiotic prescription and clinical entities associated with each location.
Nils Rosén von Rosenstein and neonatal jaundice in the 18th century
Authors: Willy Ruud Hansen Thor
Published: August 2010

Background: Nils Rosén von Rosenstein (1706–1773) was a Swedish nobleman and a professor at Uppsala University. His series of lectures on children's diseases and their treatment was published in 1764 under the title Underrättelser om Barn‐Sjukdomar och Deras Bote‐Medel. Materials and methods: Rosén von Rosenstein's book was translated into several languages. The present paper deals with the opinions and advice proffered on the jaundiced neonate in chapter 25 of the Danish edition from 1769. Results: The distinction between jaundice in the neonate and jaundice in older children is not clear everywhere in the chapter, and much of Rosén von Rosenstein's advice on therapy appears to be intended for all age groups. Rosén von Rosenstein believed that neonatal jaundice was less common in Sweden than elsewhere, and ascribed this to the common practice of purging newborns with a manna sugar laxative. The principal cause of jaundice, according to Rosén von Rosenstein, was bile stasis. When milk curdled in the stomach, the curds could plug the common bile duct, and bile would be forced into the lymphatics and from there into the blood. Thus, the bile was carried around the body and caused the skin and the sclera, as well as other organs, to become yellow. Cure was usually easy—a laxative in the form of puréed manna with powdered rhubarb was what Rosén von Rosenstein recommended.

Conclusion: Rosén von Rosenstein's opinions and advice concerning neonatal jaundice were not original, and did not differ from those found in other medical texts from the 18th and 19th centuries. The bile stasis explanation for all kinds of jaundice, including neonatal jaundice, was widely held in the 18th century, and continued to predominate in paediatric texts until the end of the 19th century. Similarly, laxatives and enemas as the cure‐all for many ailments held sway until the late 1800s.
Congenital chylothorax associated with isolated congenital hypoplastic superior caval vein: A case report
Authors: Lee Chune‐Yi , Jan Sheng‐Ling , Wang Teh‐Ming , Chi Ching‐Shiang
Published: August 2010

Congenital absence, or hypoplasia, of the superior vena cava (SVC) with situs solitus is quite uncommon. Most cases have been found incidentally and concomitant with left persistent SVC or other cardiac disorders. Congenital chylothorax may be associated with cardiac anomalies, various syndromes, thoracic ductal or venous thrombosis, birth trauma or local compression of the thoracic duct, but it is rarely caused directly by congenital SVC anomalies.

Conclusion: We report a rare case of congenital chylothorax associated with isolated congenital hypoplastic SVC and underdeveloped collateral circulation.
Low soluble Fas (sFas) and sFas ligand (sFasL) content in breast milk after preterm as opposed to term delivery
Authors: Jochum F , Loui A , Weber A , Felderhoff‐Mueser U , Bührer C , Dudenhausen JW , Obladen M
Published: August 2010

Aim: Various mechanisms of innate immunity and gastrointestinal integrity are potentially affected by soluble Fas (sFas) and sFas ligand (sFasL). Assuming that sFas and sFasL in milk reflect cellular events during lactogenesis, we aimed to assess the impact of premature parturition and duration of lactation on the concentrations of sFas and sFasL in human milk. Patients and methods: The content of the soluble form of the cell surface receptor Fas (sFas) and its natural ligand (sFasL) was measured in human breast milk of 44 healthy mothers after preterm (<35 wk, n=21) and term (>37 wk, n=23) delivery. Milk was furthermore classified as immature breast milk (days 4–7 of lactation) or mature breast milk (days 35–45 of lactation). Breast milk (2–3 ml) was sampled 5 min after the start of breastfeeding by manual expression or milk pump, and stored at −20°C until analysis by an ELISA. Results: sFas and sFasL concentrations were lower in immature milk after preterm compared to term delivery (sFas: 1.71; 1.38–2.47 ng/ml vs 3.03; 2.02–4.30 ng/ml, p<0.001; sFasL: 0.13; 0.07–0.21 ng/ml vs 0.29; 0.15–0.60 ng/ml, p<0.001 [median ± interquartile range]). Mature milk samples, taken 1 mo later from both gestational groups, did not differ in sFas/sFasL content. Soluble Fas was positively correlated with sFasL in the same sample of immature (p<0.001) and mature human milk (p<0.05). A positive correlation was found between sFas and sFasL in immature and mature milk samples of the same mother (p<0.01). The body mass index of the mothers and duration of pregnancy were positively correlated with the sFas and sFasL content in immature milk (p<0.05 and p<0.01, respectively) but not in mature milk.
Respiratory syncytial virus infection in children hospitalized for wheezing: Virus‐specific studies from infancy to preschool years
Authors: Kotaniemi‐Syrjänen Anne , Laatikainen Aino , Waris Matti , Reijonen Tiina M , Vainionpää Raija , Korppi Matti
Published: August 2010

Aim: To evaluate whether the presence of immunoglobulin G (IgG) antibodies against respiratory syncytial virus (RSV) in early childhood is associated with later asthma, and to evaluate a new diagnostic test for RSV, reverse‐transcription polymerase chain reaction (RT‐PCR), comparing it to the antigen and antibody assays initially used in RSV diagnostics in the present cohort. Methods: At the start of the study in 1992–1993, RSV was studied by antigen detection (using time‐resolved fluoroimmunoassay) and complement‐fixing antibody assay. Advances in methodology allowed us to supplement RSV studies by RT‐PCR in frozen nasopharyngeal aspirates obtained on admission, and by specific IgG antibodies (using enzyme immunoassay) in frozen serum samples obtained during the follow‐up. Results: On admission, 29 of the 100 children hospitalized for wheezing at <2 y of age were RSV positive. When compared with conventional methods, the sensitivity of RT‐PCR was 83% (100% w.r.t. antigen detection) and its specificity was 92% in diagnosing RSV infection. RSV‐specific IgG antibody concentrations rose with age, but were not predictive of asthma at any age. In the present cohort, wheezing without RSV was particularly associated with increased risk for later childhood asthma.

Conclusion: Hospitalization for wheezing in infancy is associated with increased risk for later childhood asthma, particularly in children without RSV infection on admission, although children with RSV have also slightly increased risk for later asthma. However, mere serological evidence of RSV infection is not associated with the development of asthma. In addition to RSV, more attention should be paid to less virulent agents in order to find those wheezing infants who are at particular risk of later childhood asthma.
Short‐term outcome in infants with a birthweight less than 501 grams
Authors: Rieger‐Fackeldey E , Schulze A , Pohlandt F , Schwarze R , Dinger J , Lindner W
Published: August 2010

Aim: To report survival and morbidity until discharge in preterm infants < 501 g with life support started immediately after birth. Methods/study design: Cohort study of all preterm infants with birthweights < 501 g born in three tertiary perinatal centres between 1 January 1998 and 31 December 2001 (gestational age (GA) 25.2 [21.0–30.7] wk; birthweight 435 [290–500] g; median [range]). Results: A total of 107 infants with birthweights<501 g were born. Twenty‐nine were stillborn. A prenatal decision to initiate life support immediately after birth was reached in 9/37 (24%) infants<24.0 wk GA and in 39/42 (93%) infants 24.0 wk GA. Survival was 3/37 (8%) and 26/41 (63%) in infants<24 wk GA and 24.0 wk GA, respectively. Twenty‐nine of the 48 infants with immediate life support (60%) survived (95% CI: 46–75%). Forty‐two of these 48 (88%) infants were small for gestational age. No infant without immediate life support survived (0/30). Twenty‐three (79%) survivors developed chronic lung disease (CLD) and eight (28%) received photocoagulation for retinopathy of prematurity (ROP).

Conclusion: In this population of extremely low birthweight infants, survival was higher than in previous studies when life support was provided immediately after birth. Short‐term morbidity was similar to other studies. The presented data on survival support our concept to offer immediate life support after birth in preterm infants with birthweights<501 g. The long‐term outcome of these infants needs to be assessed urgently.
Upper segment/lower segment ratio and armspan–height difference in healthy Turkish children
Authors: Turan Serap , Bereket Abdullah , Omar Anjum , Berber Mustafa , Ozen Ahmet , Bekiroglu Nural
Published: August 2010

Aim: The determination of body proportions is an important part of the clinical evaluation of children with short stature. The upper segment/lower segment ratio (US/LS ratio) and armspan–height difference is commonly used for this purpose. However, reference data are scarce in this respect, and available standards do not include standard deviations for the measurements. We aimed to establish the normal values for upper segment/lower segment ratio and armspan–height difference in Turkish children. Methods: In the present study, height, upper and lower segment, and armspan were measured in 1302 healthy children (3–18 y). The age‐related mean and standard deviation curves of the US/LS ratio and armspan–height difference were constructed for each sex. Results: The mean values of the US/LS ratio in boys were decreased from 1.108 at 3 y to 0.984 at 10 y. The nadir of the US/LS ratio (0.922) was reached at age 15 y. In girls, the mean value of the US/LS ratio gradually decreased to less than 1 at 9 y of age (1 y earlier than in boys). The nadir of the US/LS ratio (0.946) was reached at age 13 y in girls (2 y earlier than in boys). Armspan was shorter than height as expected in younger ages, but became slightly longer at around age 12 in girls and boys. Unlike boys, the armspan–height difference did not change much after puberty in girls.

Conclusion: US/LS ratio and armspan–height difference are practical parameters and easy to perform in any setting. We hope that these standards will aid clinicians in the evaluation of children with short stature.
Mortality among persons with a history of Kawasaki disease in Japan: Can paediatricians safely discontinue follow‐up of children with a history of the disease but without cardiac sequelae?
Authors: Nakamura Yosikazu , Aso Eiko , Yashiro Mayumi , Uehara Ritei , Watanabe Makoto , Tajimi Morihiro , Oki Izumi , Ojima Toshiyuki , Yanagawa Hiroshi , Kawasaki Tomisaku
Published: August 2010

Aim: To clarify the question of whether patients with Kawasaki disease suffer a higher mortality rate after the incidence of the disease in comparison with age‐matched healthy individuals. Methods: Between July 1982 and December 1992, 52 collaborating hospitals collected data on all patients having a new, definite diagnosis of Kawasaki disease. Patients were followed up until 31 December 2001 or their death. The expected number of deaths was calculated from Japanese vital statistics data and compared with the observed number. Results: Of 6576 patients enrolled, 29 (20 males and 9 females) died. The standardized mortality ratio (SMR: the observed number of deaths divided by the expected number of deaths based on the vital statistics in Japan) was 1.15 (95% CI: 0.77–1.66). In spite of the high SMRs during the acute phase, the mortality rate was not high after the acute phase for the entire group of patients. Although the SMR after the acute phase was 0.75 for those without cardiac sequelae, six males (but none of the females) with cardiac sequelae died during this period; and the SMR for the male group with cardiac sequelae was 1.95 (95% CI: 0.71–4.25). The mortality from congenital anomalies of the circulatory system was elevated, but no increase in cancer deaths was observed.

Conclusion: Although it was not statistically significant, the mortality rate among males with cardiac sequelae due to Kawasaki disease appeared to be higher than in the general population. On the other hand, the mortality rates for females with the sequelae and both males and females without sequelae were not elevated.
Interferon γ and tumour necrosis factor α in relation to anaemia and prognosis in childhood cancer
Authors: Ek Torben , Mellander Lotta , Abrahamsson Jonas
Published: August 2010

This study examined whether the initial plasma levels of tumour necrosis factor α (TNFα) and interferon γ (IFNγ) in 131 children with newly diagnosed cancer were associated with haematopoietic suppression, and whether plasma levels of TNFα or haemoglobin at diagnosis affects long‐term prognosis in childhood acute lymphoblastic leukaemia (ALL).

Conclusions: IFNγ, and possibly also TNFα, were related to anaemia in children with solid tumours. Neither TNFα levels nor Hb levels were associated with increased risk of ALL relapse.
Biliary atresia research is crossing national and interdisciplinary borderlines by the European Biliary Atresia Registry (EBAR)
Authors: Petersen Claus , Melter Michael , Leonhardt Johannes , Becker Thomas , Harder Dörte
Published: August 2010

The European Biliary Atresia Registry (EBAR) was founded in 2001 in order to raise awareness of the rare disease biliary atresia and to reinforce international and interdisciplinary cooperation. The number of participating centres and registered patients increases continuously. EBAR activities can be found at the website http://www.biliary‐atresia.com. A first evaluation of the EBAR data is scheduled for 2006, when the registry will alter its infrastructure. This meeting will be organized together with the European Federation for Biliary Atresia Research (EFBAR), a scientific committee, which was founded in 2003. The objectives of this association are to create clinical and basic research studies, which are based on existing registries in Europe.
Severe food‐allergic reactions in children across the UK and Ireland, 1998–2000
Authors: Colver Allan F , Nevantaus Heidi , Macdougall Colin F , Cant Andrew J
Published: August 2010

Aim: Medical and lay concerns about food allergy are increasing. Whilst food allergy may be becoming more common, fatal reactions to food in childhood are very rare and their rate is not changing. We sought to establish how common severe reactions are. Methods: Prospective survey, 1998 to 2000, of hospital admissions for food‐allergic reactions—conducted primarily through the British Paediatric Surveillance Unit, covering the 13 million children in the United Kingdom and Ireland. Results: 229 cases reported by 176 physicians in 133 departments, yielding a rate of 0.89 hospital admissions per 100 000 children per year. Sixty‐five per cent were male, 41% were under 4 y and 60% started at home. Main allergens were peanut (21%), tree nuts (16%), cow's milk (10%) and egg (7%). Main symptoms were facial swelling (76%), urticaria (69%), respiratory (66%), shock (13%), gastrointestinal (4%). Fifty‐eight cases were severe. Three were fatal, six near fatal, and 8 of these 9 had asthma with wheeze being the life‐threatening symptom. Three near‐fatal cases received excess intravenous epinephrine. None of the non‐fatal reactions resulted in mental or physical impairment. Seven of 171 non‐severe and 6/58 severe cases might have had a worse outcome if epinephrine auto‐injectors had been unavailable. Six of the severe cases might have benefited if auto‐injectors had been more widely prescribed.

Conclusion: In the United Kingdom and Ireland, the incidence of severe reactions is low. The study highlights that: asthma is a strongly significant risk factor for a severe reaction and therefore warrants optimal management; severe wheeze is a prominent feature of severe reactions and warrants optimal management; intravenous epinephrine should be used with great care if needed. Epinephrine auto‐injectors do not always prevent death, but our study design and data do not allow a definite statement about whether overall they are beneficial.
Chlamydia pneumoniae infection predicts a reduced risk for subsequent atopic disease
Authors: Normann Erik , Gnarpe Judy , Gnarpe Håkan , Wettergren Björn
Published: August 2010

Aim: To investigate long‐term effects on children previously infected with Chlamydia pneumoniae. Methods: A follow‐up questionnaire was sent to all participants from a former population‐based study in order to investigate health status during the 4 y that had elapsed between the two studies. In the original study, the prevalence of C. pneumoniae infection was 23% as determined by PCR analyses on throat swab specimens. These PCR results were found to have no detectable correlation for clinical disease. The main outcome measures in this follow‐up study were the reported prevalence of respiratory tract infections, asthma and allergy. Results: Approximately 83% completed the follow‐up questionnaire. No increase in respiratory tract infections was reported by children previously found to have C. pneumoniae infection. A diagnosis of allergy was more common in the former PCR‐negative population (13.4% vs 4.7%, p<0.03). The differences were most apparent in the population with atopic heredity. In a logistic regression model with different suggested risk factors for allergy, earlier infection with C. pneumoniae reduced the risk for allergy (OR=0.13; 95% CI: 0.02–0.99). This was not found for asthma.

Conclusion: A positive PCR test for C. pneumoniae in young children was associated with a lower risk of developing allergic airway disease in this study population, and did not predict an increase in respiratory tract infections.