bluuebunny/crossref_metadata_2025 huggingface dataset:
Appropriate prophylaxis with restrictive palivizumab regimen in preterm children in Sweden
Authors: Navér L , Eriksson M , Ewald U , Linde A , Lindroth M , Schollin J
Published: August 2010

Aim: Palivizumab (Synagis®) was registered in Sweden in 1999 for prophylaxis against respiratory syncytial virus (RSV) in premature infants. The high costs and the limited knowledge of the efficacy of this substance have led to debate about how and when it should be used. National guidelines for the use of palivizumab in Sweden were constructed in the year 2000. The aim of this study was to evaluate the guidelines. Methods: A nation‐wide prospective study was conducted during the two RSV seasons of the years 2000–2002. The paediatric departments in Sweden reported the use of palivizumab, the indication for its use, and the number of infants born preterm before 36 wk of gestation and less than 2 y old who were admitted to hospital for RSV infection. Results: During the two seasons, 218 (3.8%) children who were born before 36 wk of gestation, and 97 (5.4%) who were born before 33 wk, were hospitalized because of RSV infection. Five children were treated with mechanical ventilation. No death caused by RSV was reported. A total of 390 children were treated with palivizumab, and 16 (4.1%) of those who received prophylactic treatment were admitted to hospital with RSV infection.

Conclusion: We consider the comparatively restrictive Swedish recommendations to be safe and recommend that palivizumab should also be used very restrictively in the future. In our opinion, palivizumab in preterm children could be recommended only for those with chronic lung disease younger than 1 y of age, and with active treatment for their disease.
Milk consumption during pregnancy and infant birthweight
Authors: Ludvigsson JF , Ludvigsson J
Published: August 2010

Aim: To examine the risk of low birthweight (>2500 g, LBW), intrauterine growth retardation (IUGR) and preterm birth (gestational age >37wk) in relation to milk intake. Methods: Observational study in southeast Sweden. Questionnaires were used to collect data on milk consumption during pregnancy and infant birthweight from mother‐infant pairs during a 2‐y period as part of the ABIS (All Babies in Southeast Sweden) study. Data on IUGR were obtained through the Swedish medical birth registry. Results: Adjusting for confounders, low milk intake during pregnancy was associated with an increased risk of IUGR (p= 0.019; n= 12880). LBW (p= 0.191) and preterm birth (p= 0.921) were not associated with milk intake during pregnancy.

Conclusion: This study indicates that low milk intake in the pregnant mother may be associated with IUGR of the newborn. We cannot exclude the possibility that the correlation found between milk consumption and intrauterine growth may be due to undetected confounders. Hence, further research is needed to evaluate the relationship between low milk intake, birthweight and risk of IUGR.
Effects of maternal cigarette smoking and cocaine use in pregnancy on fetal response to vibroacoustic stimulation and habituation
Authors: Gingras JL , Mitchell EA , Grattan KJ , Stewart AW
Published: August 2010

Background: Cigarette smoking and cocaine use in pregnancy are common in the US and both are risk factors for sudden infant death syndrome (SIDS). Although the cause of SIDS is not known, one postulated mechanism involves abnormalities of arousal and arousal regulation. Cigarette smoking and cocaine use may cause deficits of arousal. Many believe arousal deficits occur prenatally.Aims: The aim of this study was to assess the effects of cigarette smoke and cocaine exposure during pregnancy on measures of fetal arousal and arousal competency: 1) the fetal response to vibroacoustic stimulation (VAS) and 2) habituation to VAS.Hypothesis: Maternal cigarette smoking and cocaine use in pregnancy are associated with altered arousal and arousal regulation in the fetus.Methods: Three groups of mother‐fetal dyads were enrolled: 1) cigarette smokers (n= 54), 2) cocaine users (n= 30), and 3) controls (n= 60). One hundred eight fetuses were tested at 29–31 wk gestation, 119 at 32–35 wk, and 118 at 36+ wk. The fetal response to VAS was assessed using real‐time ultrasound and a paradigm of arousal responsiveness. Responders were tested with repeated VAS to assess habituation. Also, the quality of fetal reactivity to repeated stimuli was assessed as a measure of arousal and arousal regulation competence (Behavioral Reactivity Scale).Results: The control group had a larger proportion of fetuses who were too active to initiate testing (“too active to test”) (p= 0.013); the proportion of fetuses too active to test decreased with increasing gestational age. The majority of the fetuses who could be tested responded to the initial VAS, and there were no group differences. The proportion of fetuses that habituated and the rate of habituation did not differ between the groups. Behavioral reactivity did not differ between groups.

Conclusions: The original hypotheses were not confirmed. However, the chosen assessment paradigms may have lacked sensitivity. The proportion of fetuses that were “too active to test” decreased with gestational age. The control group had a larger proportion of fetuses that were “too active to test” compared with the exposure groups. We speculate that these findings indicate that prenatal exposure to these neuroteratogens may have produced an acceleration of the behavioral response to vibroacoustic stimulation.
Indoor exposures and recurrent wheezing in infants: a study in the BAMSE cohort
Authors: Emenius G , Svartengren M , Korsgaard J , Nordvall L , Pershagen G , Wickman M
Published: August 2010

Aim: The aim of this study was to examine the relationship between indoor exposures and the home environment, and the development of recurrent wheezing during infancy. Methods: A birth cohort, comprising 4089 children, was followed. Information on exposures was obtained shortly after birth, and episodes of wheezing were recorded when the infants were 1 and 2 y of age. In a nested case‐control study, 181 infants were enrolled, who had three or more reported episodes of wheezing after 3 mo of age combined with either use of inhaled steroids or symptoms of bronchial hyper‐reactivity, and 359 age‐matched controls. Home inspections were performed during the winter following enrolment, and indoor conditions were measured. Results: Adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated. The OR for recurrent infant wheezing associated with signs of dampness reported prospectively by parents was 1.4 (0.9–2.2), and the OR for observed signs of dampness at home inspections was 1.6 (1.0–2.5). A trend was found in the risk of recurrent wheezing in relation to the number of indicators of dampness: OR 1.3 (0.8–2.2) for one sign of dampness and OR 2.7 (1.3–5.4) for three or more signs of dampness. Newly painted surfaces in the child's bedroom was associated with an increased OR for recurrent wheezing: 1.7 (1.3–2.6).

Conclusion: Indicators of dampness, as well as recently repainted interior surfaces, appear to be associated with recurrent infant wheezing, with a strengthened effect of combined indoor exposures.
Aicardi‐Goutières syndrome: clinical and neuroradiological findings of 10 new cases
Authors: Abdel‐Salam GMH , Zaki MS , Lebon P , Meguid NA
Published: August 2010

Aim: To describe the clinical and neuroimaging findings in new cases with Aicardi‐Goutières syndrome (AGS) from Egypt. Methods: Ten patients with progressive encephalopathy, bilateral calcification of the basal ganglia and spastic quadriplegia were described. Feeding difficulties, irritability, unexplained episodic fever and acrocyanosis were also observed. They were diagnosed as AGS after excluding possible non‐genetic causes (especially TORCH) and because of the high interferon‐α (IFN‐α) level in cerebrospinal fluid (CSF) in two children who underwent this specific investigation. Results: Six patients had postnatal microcephaly. Putamen was by far the most common site of calcification (nine cases) inside the basal ganglia. Calcifications were extended to the white matter, periventricular and cerebellum in three cases. Brain atrophy and/or white matter demyelination were evident in most of the cases. Further, hypogenesis of corpus callosum was detected in two cases; one of them had in addition cerebellar hypoplasia, atrial septal defect (ASD) and horseshoe kidney. To the best of our knowledge, the association of these congenital abnormalities has not been reported before in AGS. Eight families were consanguineous.

Conclusion: This paper presents variability in both age of onset, clinical picture and neuroimaging findings even in the same family, comprising new congenital abnormalities associated with AGS and subsequently expanding the spectrum of heterogeneity. The observation of familial cases and both affected males and females emphasized the major role of the single gene inheritance.
Children younger than 4 years and their substance‐dependent mothers in the child welfare clinic
Authors: Savonlahti E , Pajulo M , Helenius H , Korvenranta H , Piha J
Published: August 2010

Aim: To explore the prevalence of substance dependency among mothers of small children and to evaluate the value of a routine‐style maternal report on social support, child's somatic health history and child caregiving experiences to differentiate the substance‐dependent group from the non‐dependent group. Methods: Mothers (n= 413) of children less than 4 y in the child welfare clinics filled in the Substance Abuse Subtle Screening Inventory (SASSI, Miller 1985) and questionnaires concerning social support, somatic history of the child, difficulties in social environment and in caring for the child. Results: The prevalence of substance dependency was 5.8%. The maternal perceptions of the child's somatic history could not differentiate the dependent from the non‐dependent group, while the child caregiving difficulties were more often present in the group of substance‐dependent mothers. The combined group of substance dependency and substance use was significantly associated with low social support and difficulties in social environment.

Conclusions: The prevalence of substance dependency among mothers of small children is considerable and significantly associated with child caregiving difficulties and low social support, while the perceptions on the somatic health of the child did not differentiate the dependent from the non‐dependent group. This suggests the value of considering the maternal experiences in caring for the child and well‐being of the mother during check‐ups in the child welfare clinic in order to identify the mother‐child pairs at risk.
A genetic reason for male excess in infant respiratory mortality?
Authors: Finnström Orvar
Published: August 2010

Male infants have a 50% higher risk of death from respiratory diseases and a number of congenital heart diseases that can lead to cerebral hypoxia. The most important of these diseases are infant respiratory distress syndrome and sudden infant death syndrome.

Conclusion: The mechanism behind the excess peri‐mortality rate in male infants is not known. A genetic factor leading to reduced tolerance to hypoxia is possible.
Reduced gains in fat and fat‐free mass, and elevated leptin levels in children and adolescents with cystic fibrosis
Authors: Ahmed ML , Ong KK , Thomson AH , Dunger DB
Published: August 2010

Aim: Bodyweight is an important prognostic indicator in children with cystic fibrosis (CF), but the relationships between body composition and clinical outcomes are less clear. We have investigated the role of leptin (a potential satiety factor) and changes in body composition, height and weight with respect to age and clinical outcome. Methods: 143 children (77 boys) with CF and a median age (range) of 5.99 (2.27–17.98) y were followed with annual measurements of height, weight, skinfolds, forced expiratory volume (FEV1), Shwachman score assessment and fasting blood sample. Our control group comprised 40 children (20 boys, 20 girls) aged 8.6–10.2 y at recruitment who were participating in a longitudinal study of growth and puberty. Results: SD scores for height, weight and BMI decreased with age; fat and fat‐free mass was lower in both sexes compared to controls. Shwachman score decreased with age in both sexes and was related to fat‐free mass in girls, and to both fat‐free and fat mass in boys. FEV1 decreased with age only in boys and was related to fat‐free mass. Leptin levels by age and by fat mass were higher in CF children compared to controls.

Conclusion: Despite improvements in management, contemporary children with CF still gain less body fat and fat‐free mass and are shorter than controls. The higher leptin levels we observed may be due to stimulatory effects of inflammatory cytokines and we postulate that they may contribute to the anorexia, poor weight gain and growth of these children.
Prevalence of germline mutations in the TSH receptor gene as a cause of juvenile thyrotoxicosis
Authors: Lavard L , Jacobsen B Brock , Perrild H , Vassart G , Parma J
Published: August 2010

Aim: To ascertain the prevalence of germline mutations in the TSH receptor gene as a cause of juvenile thyrotoxicosis (JT) in non‐autoimmune patients. TSH receptor gene mutations are not seen in autoimmune‐active patients. Methods: In a nationwide study on JT, 123 patients were re‐examined 10 y (range 4 to 21 y) after diagnosis. Two patients with toxic adenoma were excluded. In 25 patients, no TPO, TG or TSH‐R antibodies were found. In 17 patients, DNA material was available for TSH receptor gene analysis. The entire TSH receptor gene was sequenced in five patients. TSH receptor “hot spots” for mutations in exon 9 and 10 were sequenced in the remaining 12 patients. Results: A TSH receptor gene germline mutation was identified in only one patient of a total number of 121 patients with JT, of which 17 patients were presumed to have non‐autoimmune JT by the lack of thyroid autoantibodies.

Conclusion: In Denmark the prevalence of germline mutations in the TSH receptor gene is one in 121 patients with JT (0.8%; 95% CI: 0.02–4.6%) and one in 17 patients with presumed non‐autoimmune JT (6%; 95% CI: 5.88% (0.15–28.69)).
The fifty percent male excess of infant respiratory mortality
Authors: Mage DT , Donner EM
Published: August 2010

Aim: To test whether infant mortality from clearly respiratory causes has a consistent male excess that is different from the male excess in most cardiac conditions. Methods: Analysis of male excess in infant mortality data from the United States and from north European countries. Data are analyzed for the period 1979–2002 in autopsied and unautopsied cohorts. Results: Several modes of respiratory death in infancy are characterized by an approximate 50% male excess. This common excess is demonstrated in vital statistics for infant respiratory distress syndrome, sudden infant death syndrome, inhalation of food and other objects causing obstruction of respiratory tract or suffocation, congenital pneumonia, viral pneumonia, bronchiolitis and bronchitis, and accidental drowning. Results are presented for these and other respiratory causes of mortality in all United States infant deaths from 1979–1998 and for sudden infant death syndrome from the United Kingdom and Scandinavia. In sudden infant death syndrome, the common male excess appears to exist only for the autopsied post‐neonatal cases. Comparisons are made to the male excess mortality from congenital cardiac anomalies showing a similarly large male excess for those conditions resulting in severe hypoxic and ischemic hypoxia.

Conclusion: Because these respiratory disease conditions are quite different, it is proposed that their common ∼50% male excess implies a common terminal hypoxic condition and mechanism of death reached via the different pathways. We hypothesize that an unknown X‐linkage may be responsible for this consistent male excess in infant mortality.
Clinical, biochemical and molecular analyses of six patients with isolated cytochrome c oxidase deficiency due to mutations in the SCO2 gene
Authors: Vesela K , Hansikova H , Tesarova M , Martasek P , Elleder M , Houstek J , Zeman J
Published: August 2010

Background and aim: Cytochrome c oxidase (COX) deficiency represents a heterogeneous group of disorders. Numerous proteins are required for efficient COX assembly and maintenance. In 26 children with isolated COX deficiency, we studied mutations in the SCO2 gene, which is involved in the copper transport into the inner mitochondrial membrane, and we analysed the clinical and biochemical consequences of SCO2 mutations. Methods: The activities of respiratory chain complexes were measured spectrophotometrically in isolated mitochondria and/or crude cell extracts in all available tissues. Two‐dimensional polyacrylamide electrophoresis (2D‐PAGE) was used to separate the complexes and their subunits. The mutations were detected by sequencing and RFLP analysis. Results: Mutations in the SCO2 gene were found in six children. Early neonatal onset of hypertrophic cardiomyopathy and encephalopathy were observed in one boy with compound heterozygous mutations C1280T and G1541A. In all five children with homozygous mutation G1541A, progressive encephalopathy developed between 2 and 6 mo of age. Isolated COX deficiency was found in the skeletal muscle, heart, liver and brain but not in fibroblasts. 2D‐PAGE in the skeletal muscle showed markedly decreased amounts of all COX subunits.

Conclusion: Our results suggest that mutations in the SCO2 gene are not rare, at least in our population. Although clinical symptoms may rely on the type of SCO2 mutation, the prognosis is unfavourable in all patients.
Oral hypertonic glucose spray: a practical alternative for analgesia in the newborn
Authors: Akçam M , Örmeci AR
Published: August 2010

Aim: Pain and stress have been shown to induce significant physiological and behavioural reactions in newborn infants. Pharmacological agents are not recommended in neonates for pain relief in minor procedures. Since different sweet solutions given orally by syringe have been shown to relieve pain in neonates, we decided to compare the analgesic effects of a small dose of glucose solution given orally by spray and by syringe during heel lancing in term neonates, using a validated behavioural acute pain rating scale. Methods: Sixty hyperbilirubinaemic full‐term neonates were studied. We used a randomized, masked, placebo‐controlled, crossover trial. Each infant was assessed three times receiving 0.5 ml 30% glucose in spray form, 0.5 ml 30% glucose by syringe or 0.5 ml sterile water by syringe in random order, 2 min before heel lancing. Results: Pain scores were significantly lower in the 30% glucose given either spray or syringe groups compared with the placebo group. No statistically significant difference in pain scores was found between the 30% glucose spray group and 30% glucose syringe group.

Conclusions: A small dose of 0.5 ml 30% glucose spray has an equal analgesic effect to the same dose given by syringe. The spray form has the advantage of being easy to use and is well accepted by newborn babies.
Clinical features and epidemiology of septicaemia and meningitis in neonates due to Streptococcus agalactiae in Copenhagen county, Denmark: a 10 year survey from 1992 to 2001
Authors: Andersen J , Christensen R , Hertel J
Published: August 2010

Aim: To elucidate the clinical and biochemical features, and to estimate the incidence and outcome of invasive culture‐verified group B streptococcal (GBS) septicaemia/meningitis in neonates in Denmark. Methods: Clinical microbiology laboratory records in patients 0–3 mo of age were searched for culture‐verified GBS during 1992–2001 in Copenhagen County. Clinical records at the neonatal intensive care unit were reviewed retrospectively. Selected clinical and biochemical parameters were evaluated. Results: 61 neonates had culture‐verified GBS septicaemia/meningitis. The mean annual incidence was 0.76 cases per 1000 livebirths (range 0.0–1.91). A significant decrease in incidence was observed in the latest 3 y. The male:female ratio was 1.3:1. Eighty percent of the neonates had early‐onset GBS within 24 h, 57% with symptoms at birth. Predominant initial symptoms were respiratory (72%), cardiovascular (69%) and neurological (63%). Only 4% developed GBS by day 7–90. Seventy‐five percent had maternal or neonatal risk factors for early‐onset GBS disease; 21% had clinical asphyxia, 37% of the mothers had premature rupture of membranes and 31% of the mothers were febrile. Initial C‐reactive protein (CRP) was low, but increased significantly after more than 12 h duration of symptoms in 82% of patients. Leucopenia was an important initial haematological marker.

Conclusion: The incidence of early‐onset GBS has decreased significantly in Denmark, probably because of preventive measures in pregnancy and during birth. Respiratory symptoms are early signs of early‐onset GBS. Initial leucopenia and a late (12–48 h) increase in CRP are valuable markers for invasive GBS.
Translating knowledge into practice in the “post‐genome” era*
Authors: Scriver CR
Published: August 2010

The Human Genome Project is “completed”, but it is only a beginning in the understanding of genomic structure and function. A “human phenome project” is waiting in the wings. The complexity involving a phenotype can be glimpsed, for example, if one enquires into the relationships between mutant phenylalanine hydroxylase (PAH) genotypes and the clinical disorders called PKU /Hyperphenylalaninemia—so called lessons from PKU genotypes and phenotypes. Since genomes speak biochemistry, not phenotype (said RHA Plasterk), for genomics to penetrate medicine, biochemistry and biology must be allies.

The ideal translators and ambassadors of the knowledge that must cross the gap between laboratory and bedside are the clinician scientists; restoration of that attenuated community of colleagues is a necessary step in the implementation of genomic medicine.
Are our children fit or fat?
Authors: Viikari J
Published: August 2010

Overweight and obesity are increasing in Swedish boys and girls aged 7‐16 y. The fitness of 16‐y‐old Swedish boys in 2001 was approximately 10% worse than in 1987.

Conclusion: It is important to start the prevention of atherosclerosis and type 2 diabetes early. The number of children with physical inactivity and obesity should be as low as possible.
Antenatal renal pelvis dilatation emphasizing vesicoureteric reflux: two‐year follow‐up of minor postnatal dilatation
Authors: Kapadia H , Lidefelt K‐J , Erasmie U , Pilo C
Published: August 2010

Aim: To describe the occurrence of foetal renal pelvis dilatation in an unselected population of pregnancies and to describe the clinical course in a subgroup of infants with minor renal pelvis dilatation (RPD). Methods: During 1996–1999 the foetuses of 17850 consecutive pregnant women were scanned with ultrasonography (USG) in the 16th–19th gestational week and later in the pregnancy when indicated. RPD was defined as anterior–posterior pelvic diameter ≤5mm. After birth all infants were examined with USG twice. If any postnatal USG showed RPD ≤10mm, extended radiological investigation was performed. Infants with pelvis dilatation <10 mm and no calyceal or ureteric dilatation were not investigated further and antibiotic prophylaxis was discontinued. The children were followed up at 2 y of age. Results: 109 foetuses (0.6%) with RPD were identified. Postnatally, 94/109 were available for follow‐up: 43 had postnatal dilatation ≤10 mm and were investigated and treated according to clinical routine, while 51 had dilatation < 10 mm and were followed up after they had reached at least 2 y of age. No case of pyelonephritis was recorded. USG in 48/51 children was normal.

Conclusion: The data indicate that infants with minor RPD do not constitute a risk group for renal morbidity and thus do not need antibiotic prophylaxis and extensive radiological examination.
Clinical signs of heart failure are associated with increased levels of natriuretic peptide types B and A in children with congenital heart defects or cardiomyopathy
Authors: Westerlind A , Wåhlander H , Lindstedt G , Lundberg P‐A , Holmgren D
Published: August 2010

Aim: To study whether natriuretic peptide types B (BNP) and A (ANP) reflect clinical signs of heart failure (CSHF) in children with congenital heart defects or cardiomyopathy resulting in different types of haemodynamic situations, such as pressure overload in coarctation of the aorta (CoA), volume overload in ventricular septal defect (VSD) or systolic dysfunction in dilated cardiomyopathy (DCM). Methods: Blood samples for plasma P‐BNP and P‐ANP were taken before procedures during regular investigation from 26 children (9 CoA, 11 VSD and 6 DCM). The ordinary paediatric cardiologist performed the cardiac evaluation and the data were retrieved from medical charts. CSHF was considered positive if two of the following criteria were fulfilled: reduced physical capacity, feeding disorders, dyspnoea, tachypnoea, hepatomegaly and oedema. The statistical methods were non‐parametric. Results: 0/9 children with CoA, 5/11 with VSD and 6/6 with DCM had CSHF. In children with CSHF, P‐BNP and P‐ANP were higher, 263 ng l−1 (range 47.5–1300) and 303 ng l−1 (range 168–466), than in those without CSHF, 12.3 ng l−1 (range 4.8–30.8) and 42.9 ng l1 (range 13.7–189), respectively (p < 0.001, Mann‐Whitney U‐test), irrespective of the diagnosis. The same relationship was also found in the group of children with VSD.

Conclusion: Plasma levels of ANP and BNP increase in children with CSHF. This increase is seen irrespective of whether it is due to systolic dysfunction, as in children with DCM, or to a volume overload with a normal systolic function, as in children with VSD.
Lymphadenitis cervicalis due to Mycobacterium interjectum in immunocompetent children
Authors: Rose M , Kitz R , Mischke A , Enzensberger R , Schneider V , Zielen S
Published: August 2010

This report presents two cases of cervical lymphadenitis due to Mycobacterium interjectum in healthy young children, identified by sequencing of the 16S rRNA gene. Surgical resection combined with chemotherapy resulted in cure.

Conclusion: The attention of clinicians needs to be drawn to an emerging mycobacterial pathogen which might be overlooked or misidentified in routine laboratory testing.
Congenital self‐healing reticulohistiocytosis: report of a case and review of the literature
Authors: Ricart J , Jimenez A , Marquina A , Villanueva A
Published: August 2010

Congenital self‐healing reticulohistiocytosis (CSHRH), a rare disorder initially seen at birth or in the newborn period, is characterized by spontaneously involuting skin lesions. We present the case of a 12‐d‐old female who was born with many red‐brownish nodules scattered over her entire body, and which regressed spontaneously.

Conclusion: Although there are no clues to differentiate CSHRH from Letterer‐Siwe disease, some signs and symptoms might enable us to reach an accurate diagnosis. A long‐term follow‐up to detect evidence of relapse or progression of the disease would be well advised.
Sleep patterns in children and adolescents with functional recurrent abdominal pain: objective versus subjective assessment
Authors: Haim A , Pillar G , Pecht A , Lerner A , Tov N , Jaffe M , Hardoff D
Published: August 2010

Aim: To document objective sleep patterns of children and adolescents with functional recurrent abdominal pain (RAP), and to compare them with subjective sleep assessments and sleep patterns of healthy controls. Methods: Subjective sleep reports and sleep habit assessments were obtained from 25 adolescents with functional RAP and from 15 age‐ and gender‐matched healthy volunteers, and were compared with continuous movement monitoring using the Actigraph for 7 consecutive days. Results: Abdominal pain before falling asleep was a unanimous complaint in the RAP group, with 29% reporting awakening from sleep by the pain. Only 25% of RAP patients assessed their sleep quality as good, compared with 87% of the control group. Objective sleep patterns measurements of the RAP patients were similar to those of the control group as well as to measurements observed in a large population of school‐aged children and adolescents.

Conclusion: This study of a small group of children and adolescents with functional RAP provides objective evidence that their sleep patterns do not differ from those of normal peers, despite their subjective complaints.
Prediction of early tolerance to enteral feeding by measurement of superior mesenteric artery blood flow velocity: appropriate‐ versus small‐for‐gestational‐age preterm infants
Authors: Pezzati M , Dani C , Tronchin M , Filippi L , Rossi S , Rubaltelli FF
Published: August 2010

Aim: To evaluate whether serial Doppler measurements of superior mesenteric artery blood flow velocity could predict early tolerance to enteral feeding in preterm infants. Methods: In a prospective study, 54 healthy preterm neonates were assigned to one of the following groups: neonates with birthweight appropriate for gestational age (group 1), neonates small for gestational age without (group 2) and with prenatal haemodynamic disturbances (group 3). We studied Doppler blood flow velocity and resistance index before and after the first feed. Results: Contrary to patients of group 3, infants in groups 1 and 2 showed a significant increase in blood flow velocity and a significant decrease in resistance index from the preprandial values after the first feed. At each postprandial time, we found significant differences in all velocity and resistance measurements between patients of group 3 and patients of both groups 1 and 2. In all patients, we found that the value of mean velocity measured 30 min after the first feed was the most predictive of early feed tolerance, with 95% sensitivity and 94% specificity when mean velocity >0.38 m/s.

Conclusion: Small‐for‐gestational‐age preterm infants with prenatal haemodynamic disturbances have an unusual intestinal haemodynamic response to the first feed. In the whole group of preterm infants, the value of mean velocity measured 30 min after the first feed is a good tool for the clinician in predicting early enteral feeding.
Pentoxyfylline in and prevention and treatment of chronic lung disease
Authors: Lauterbach R , Pawlik D , Zembala M , Szymura‐Oleksiak J , Lisowska‐Miszczyk I , Kowalczyk D , Bury J
Published: August 2010

The anti‐inflammatory effects of pentoxfylline are associated with a number of clinical benefits. These include reduction in mortality in patients who have undergone bone marrow transplants or suffer peritonitis. In infants with sepsis, a reduction in mortality has also been associated with pentoxyfylline administration. The anti‐inflammatory effects of pentoxyfylline, as well as its bronchodilator, diuretic and respiratory muscle stimulant effects suggest it may have a useful role in BPD. Interim analysis of a prophylactic trial suggests pentoxyfylline may reduce treatment requirements after the neonatal period and that, in established BPD, pentoxyfylline and dexamethasone may be of similar efficacy.
Appropriate levels of oxygen saturation for preterm infants
Authors: Askie L
Published: August 2010

Although oxygen is probably the most common therapy delivered to small or sick newborns in the past 75 years, what constitutes appropriate oxygenation for these infants remains highly controversial. The lack of direct evidence, in the form of randomised trials, of the effects of different oxygen levels on meaningful, long‐term outcomes has fuelled this controversy and contributed to the significant variation in practice currently seen. Conclusions drawn from the existing evidence regarding oxygen saturation levels for preterm infants include that retinopathy of prematurity rates may be reduced if lower saturation ranges are targeted in the early weeks of life. There is, however, no recent, good quality, trial information that has directly addressed this question. Retinopathy outcomes may also be improved if oxygen saturation is targeted higher in a subset of preterm infants with more severe eye disease in the post‐acute phase. There is now direct evidence, from randomised trials, that routine higher oxygen saturation targeting in the chronic phase confers no short‐ or long‐term growth or development benefits. Evidence is now mounting regarding the adverse pulmonary sequelae associated with routine higher, and thus longer, oxygen exposure. Information regarding oxygen saturation levels and early mortality is inconclusive. The major unanswered question that requires urgent resolution is the important long‐term effects of targeting lower versus higher oxygen saturation ranges during the first days/weeks of a preterm infant's life. Such an important clinical question can only be answered rigorously and definitively using the randomised trial methodology.
Advances in computer‐assisted single‐photon emission computed tomography (SPECT) for epilepsy surgery in children
Authors: Buchhalter JR , So EL
Published: August 2010

Epilepsy surgery has emerged as an important option in the treatment of children with epilepsy that is refractory to antiepileptic drug management. The cornerstone of successful surgery is accurate localization of the brain region of seizure onset. Traditional techniques of seizure onset localization, e.g. surface electroencephalography (EEG) recording and magnetic resonance imaging (MRI), allow accurate localization in a significant number of patients. When the focus of seizure onset is not apparent from these non‐invasive techniques, other methods of localization, e.g. intracranial EEG recording, may be needed before resection of the focus. Single‐photon emission computed tomography (SPECT) is a nuclear medicine blood‐flow technique that has been used to identify a region of epileptogenic brain associated with low blood flow in the resting state (interictal SPECT) or increased blood flow at the time of seizure activity (ictal SPECT). This report describes the validation and utility of a computer‐assisted method of subtracting the interictal from the ictal SPECT scans and co‐registering the difference image on the MRI. This method, called subtraction ictal SPECT co‐registered on MRI (SISCOM), is used in guiding the location and the extent of intracranial electrode implantation, or in obviating the need for the implantation in some cases.
Memory development and intellectual disabilities
Authors: Vicari S
Published: August 2010

Neuropsychological research has permitted different cognitive profiles among subjects with intellectual disabilities (ID) of different etiology to be defined. For example, numerous authors have stressed that the typical language profile for people with Down's syndrome (DS) consists of poor production with greater compromise of morphosyntax than of lexical abilities, but relatively preserved comprehension. Children with Williams' syndrome (WS) often show marked impairment in certain visuospatial abilities (especially praxic‐constructive) and relative preservation of both productive and receptive language, at least concerning the phonological elements. These observations seem to support a theoretical approach that considers ID not as a mere slowing of normal cognitive development, but as distinct, individual profiles that can be qualitatively specified. The importance of this approach was shown in several recent studies of memory, especially implicit memory in subjects with ID. Neuropsychological studies suggest insufficient development of the mnemic function in ID at different levels of articulation. Long‐term memory has been extensively investigated in people with ID both in the explicit and in the implicit component. According to recent studies, people with ID should show a diffuse impairment of declarative mnesic abilities and a relative preservation of implicit memory. The focus of this study is on the characteristics of long‐ and short‐term memory in children with ID and, particularly, with DS and WS. The results are relevant to knowledge on the qualitative aspects of the anomalous cognitive development in mentally retarded people and the neurobiological substrate underlying this development.
Functional studies of frataxin
Authors: Isaya G , O'Neill HA , Gakh O , Park S , Mantcheva R , Mooney SM
Published: August 2010

Mitochondria generate adenosine triphosphate (ATP) but also dangerous reactive oxygen species (ROS). One‐electron reduction of dioxygen in the early stages of the electron transport chain yields a superoxide radical that is detoxified by mitochondrial superoxide dismutase to give hydrogen peroxide. The hydroxyl radical is derived from decomposition of hydrogen peroxide via the Fenton reaction, catalyzed by Fe2+ ions. Mitochondria require a constant supply of Fe2+ for heme and iron‐sulfur cluster biosyntheses and therefore are particularly susceptible to ROS attack. Two main antioxidant defenses are known in mitochondria: enzymes that catalytically remove ROS, e.g. superoxide dismutase and glutathione peroxidase, and low molecular weight agents that scavenge ROS, including coenzyme Q, glutathione, and vitamins E and C. An effective defensive system, however, should also involve means to control the availability of pro‐oxidants such as Fe2+ ions. There is increasing evidence that this function may be carried out by the mitochondrial protein frataxin. Frataxin deficiency is the primary cause of Friedreich's ataxia (FRDA), an autosomal recessive degenerative disease. Frataxin is a highly conserved mitochondrial protein that plays a critical role in iron homeostasis. Respiratory deficits, abnormal cellular iron distribution and increased oxidative damage are associated with frataxin defects in yeast and mouse models of FRDA. The mechanism by which frataxin regulates iron metabolism is unknown. The yeast frataxin homologue (mYfhlp) is activated by Fe(II) in the presence of oxygen and assembles stepwise into a 48‐subunit multimer (α48) that sequesters <2000 atoms of iron in a ferrihydrite mineral core. Assembly of mYfhlp is driven by two sequential iron oxidation reactions: a fast ferroxidase reaction catalyzed by mYfh1p induces the first assembly step (αα3), followed by a slower autoxidation reaction that promotes the assembly of higher order oligomers yielding α48. Depending on the ionic environment, stepwise assembly is associated with the sequestration of 50–75 Fe(II)/subunit. This Fe(II) is initially loosely bound to mYfh1p and can be readily mobilized by chelators or made available to the mitochondrial enzyme ferrochelatase to synthesize heme. However, as iron oxidation and mineralization proceed, Fe(III) becomes progressively inaccessible and a stable iron‐protein complex is produced. In conclusion, by coupling iron oxidation with stepwise assembly, frataxin can successively function as an iron chaperon or an iron store. Reduced iron availability and solubility and increased oxidative damage may therefore explain the pathogenesis of FRDA.
Lack of correlation between fatty acid oxidation disorders and haemolysis, elevated liver enzymes, low platelets (HELLP) syndrome?
Authors: Holub M. , Bodamer O. A. , Item C. , Mühl A. , Pollak A. , Stöckler‐ipsiroglu S.
Published: August 2010

Aim: Fatty acid β‐oxidation defects comprise a heterogeneous group of disorders that may precipitate acute life threatening metabolic crises particularly during catabolic episodes. Several studies have demonstrated a possible association between fatty acid β‐oxidation defects, including long‐chain 3‐hydroxyacyl‐CoA dehydrogenase deficiency and severe pregnancy complications. However, the precise percentage of women with haemolysis, elevated liver enzymes, low platelets (HELLP) syndrome associated with foetal fatty acid β‐oxidation defects is not known. Methods: We carried out a multicentre retrospective study on 88 infants, born to women with HELLP syndrome. Acylcarnitine profiles from blood dried on filter paper cards were analysed by tandem mass spectrometry for the diagnosis of fatty acid β‐oxidation defects. In addition, we screened for the common long‐chain 3‐hydroxyacyl‐CoA dehydrogenase deficiency mutation using a standard restriction fragment length polymorphism polymerase chain reaction method. Results: None of the infants studied carried the common long‐chain 3‐hydroxyacyl‐CoA dehydrogenase deficiency mutation. There was no evidence of fatty acid β‐oxidation defects, including long‐chain 3‐hydroxyacyl‐CoA dehydrogenase deficiency, as expected by unremarkable acylcarnitine profiles, while three infants with fatty acid β‐oxidation defects were diagnosed in the control group.

Conclusions: Neither foetal long‐chain 3‐hydroxyacyl‐CoA dehydrogenase deficiency, including heterozygosity for the common long‐chain 3‐hydroxyacyl‐CoA dehydrogenase deficiency mutation, nor fatty acid β‐oxidation defects in general are a major risk factor for HELLP syndrome in Austria.
In vivo spectroscopy of jaundiced newborn skin reveals more than a bilirubin index
Authors: Lyngsnes Randeberg L. , Bruzell Roll E. , Norvang Nilsen L. T. , Christensen T. , Svaasand L. O.
Published: August 2010

Aim: The aims of this study were to improve the algorithms for calculating a transcutaneous bilirubin index (TcB), to follow the bilirubin concentrations during phototherapy and to evaluate possible changes in skin optical parameters such as pigmentation and erythema during phototherapy. Method: Reflectance measurements were performed on 51 jaundiced newborns, of which 10 were subjected to phototherapy. The measurements were collected with a diode array spectrophotometer with an integrating sphere accessory, and a TcB was calculated from the measured spectra using algorithms based on diffusion theory. The newborns' birthweights were 2000 g and their gestational age was 35.5 wk. They had no substantial illnesses, and no newborns were submitted to the study until their second day. Heel prick blood samples were analysed for total serum bilirubin (Sbr) by the diazo reaction method. Phototherapy equipment was either an overhead lamp or lightbed. Results: Measurements from the forehead gave the best correlation between TcB and Sbr (r=0.81, p<0.05). However, during phototherapy no significant correlation between TcB and Sbr was observed. A correlation (r=0.45, p<0.05) was found between phototherapy and melanin index obtained from the patients' back.

Conclusions: Reflectance spectroscopy is useful in assessing bilirubin concentrations before phototherapy, and can also reveal changes in skin parameters such as pigmentation occurring as a result of phototherapy.
Pulmonary haemorrhage and cardiac dysfunction in a neonate with medium‐chain acyl‐CoA dehydrogenase (MCAD) deficiency
Authors: Maclean K. , Rasiah V. S. , Kirk E. P. E. , Carpenter K. , Cooper S. , Lui K. , Oei J.
Published: August 2010

We report on a favourable case of MCAD deficiency (homozygous 985A>G) that presented as lethargy, poor feeding, pulmonary haemorrhage and cardiac arrest without hypoglycaemia. The cessation of intralipid and the commencement of carnitine supplementation were associated with a rapid clinical improvement.

Conclusion: Mild carnitine depletion and secondary impairment of long‐chain fatty acid metabolism may have contributed to post‐asphyxial myocardial dysfunction and ventricular arrhythmias. Metabolic disorders must be kept in mind as a differential diagnosis in acutely ill infants, but it must also be emphasized that carnitine therapy is not uniformly effective in all MCAD patients.
Growth and growth hormone in children born small for gestational age
Authors: Rapaport Robert , Tuvemo Torsten
Published: August 2010

Although most children born small for gestational age catch up in growth by age 2 y, up to 14% remain more than 2 standard deviations below the mean for height. Recombinant growth hormone is approved by the US Food and Drug Administration and by the European Agency for Evaluation of Medicinal Products for the treatment of children born small for gestational age who fail to manifest catch‐up growth by 2 y or 4 y, respectively.

Conclusion: We conclude from clinical studies that growth hormone therapy can induce catch‐up growth in these children.
Phototherapy: Old questions, new answers
Authors: Madan Ashima
Published: August 2010

Despite its popularity and widespread use, there remains much more to be learned about phototherapy.

Conclusion: There is continued debate on whether intermittent phototherapy is more effective than continuous phototherapy; if light of a longer wavelength is more effective than blue light phototherapy; and if phototherapy in the presence of bilirubin is toxic to normal or abnormal red blood cells. Three in vitro studies in this issue of the journal provide answers to some of these questions.
Teenage asthma after severe infantile bronchiolitis or pneumonia
Authors: Hyvärinen Mari , Piippo‐Savolainen Eija , Korhonen Kaj , Korppi Matti
Published: August 2010

Objective: The purpose of the study was to evaluate asthma at >13 y of age in children with infantile bronchiolitis or pneumonia. Methods: In 1981–1982, 127 children at <2 y of age were hospitalized for bronchiolitis (n=81) or pneumonia (n=46). Respiratory syncytial virus (RSV) infection, eosinophilia and markers of atopy were assessed and recorded on admission. At a median age of 14.9 y, atopic and asthmatic symptoms were screened by a written questionnaire in 98/127 (77%) study subjects. Results: Asthma was present, according to two definitions, in 14% to 23% in the original bronchiolitis and in 12% to 15% in the original pneumonia group. The figures were 8% to 17% in the RSV infection and 16% to 23% in the non‐RSV infection group. Early asthma‐predictive factors were repeated wheezing, atopic dermatitis and elevated blood eosinophils. All but one of the teenage asthmatics had allergic rhinitis.

Conclusion: An increased risk for asthma persists until the teenage period after bronchiolitis and pneumonia in infancy. Both early and later atopy were significant risk factors. The present study was unable to demonstrate the association between early RSV infection and teenage asthma.
Bilirubin‐induced cell death during continuous and intermittent phototherapy and in the dark
Authors: Bruzell Roll Ellen
Published: August 2010

Aim: To compare continuous and intermittent light exposure in the presence of bilirubin with respect to cellular damage. Furthermore, it was of interest to characterize the nature of cellular toxicity of bilirubin in the dark. Method: A murine lymphoma cell line, L5178Y‐R (LY‐R), was exposed to solutions of bilirubin (160 μM) supplemented with human serum albumin (200 μM) and irradiated with phototherapy light (Philips 20W/52) at a constant total dose of approximately 500 kJ/m2. The irradiation was given either as intermittent or continuous treatment with light of variable irradiance. The three lower irradiance levels were clinically relevant. Cells treated with bilirubin were also kept in the dark for various periods of time. Cell toxicity was determined by measuring apoptosis and necrosis. Apoptosis was measured by terminal deoxynucleotide transferase and propidium iodide staining assay, while trypan blue assay was used for detection of necrosis. Results: There was no difference (n=6, p>0.05) between continuous and intermittent irradiation in the induction of early and late apoptotic cell death. Necrosis was more pronounced after intermittent treatment. Bilirubin dark toxicity was observed and classified as both apoptotic and necrotic.

Conclusion: Continuous and intermittent light exposure caused the same degree of apoptotic cell death, while the cells underwent more necrotic death after intermittent exposure. Bilirubin was cytotoxic in the dark by both cell death mechanisms.