bluuebunny/crossref_metadata_2025 huggingface dataset:
Congenital heart defects: The patients who die
Authors: Meberg Alf , Lindberg Harald , Thaulow Erik
Published: August 2010

Aims: To register mortality and causes of death in patients with congenital heart defects (CHDs). Methods: Prospective population‐based observational study. Results: 553 infants with CHD (1.1% of live born) were observed for 1–22 y (median 10 7/12 y). Sixty‐four died (11.6%), of whom 32 (50%) died during the first 4 wk, and 51 (79.7%) during the first year of life. Of the total neonatal deaths in the population (3 per 1000), CHDs occurred in 21.5%. Mortality for children with CHDs was not significantly different between the cohorts born in 1982–1991 and 1992–2002, for either neonatal deaths or deaths later on (p>0.05). Out of 170 patients in whom therapeutic procedures (surgery, catheter interventions) were undertaken, 34 (20%) died. Nine cases (1.6%) died with unrecognized CHDs; seven of these on the first day of life with severe extracardiac malformations. In 50 (78.1%) cases, death was judged to be caused directly or indirectly from the CHD, and in 14 (21.9%) from extracardiac malformations or other conditions.

Conclusion: CHDs occur in a substantial number of neonatal deaths. Most deaths are caused by cardiac insufficiency. The mortality rate remained unchanged.
Human torovirus: A new virus associated with neonatal necrotizing enterocolitis
Authors: Lodha Abhay , de Silva Nicole , Petric Martin , Moore Aideen M
Published: August 2010

Aim: Toroviruses have been associated with gastroenteritis in both animals and humans. The aim of this study was to examine the fecal excretion of torovirus in infants with necrotizing enterocolitis (NEC). Methods: We reviewed all infants with NEC admitted to our tertiary care NICU over a 5‐y period who had stool specimens sent for microbial culture and virology. Infants in the NICU during the same period with diagnoses other than NEC served as controls. Results: Forty‐four infants with NEC stages I–III were identified, and pathogenic organisms were identified in 27 (61%). Toroviruses were identified in stool cultures in 48% of patients with NEC, and 17% of the non‐NEC controls (p<0.001). There was no significant difference in illness severity or mortality between the torovirus‐positive and ‐negative infants with NEC.

Conclusion: Torovirus should be added to the list of infectious agents associated with NEC in newborn infants. The exact role torovirus plays in the etiology and progression of NEC warrants further investigation.
Integrated care of childhood disease in Brazil: Mothers' response to the recommendations of health workers
Authors: Alves da Cunha Antonio JL , Dos Santos Sílvia Reis , Martines José
Published: August 2010

Aim: To describe the process of follow‐up in primary care facilities where the Integrated Management of Childhood Illness (IMCI) strategy was implemented. IMCI was developed by WHO and UNICEF as an integrated approach to manage sick children under 5 y of age and aims to reduce mortality and morbidity. Methods: From August 2001 to February 2002, 229 sick children who had a health condition included in the IMCI case management guidelines were seen in six family healthcare facilities in Brazil. We analysed the care provided to 153 children who were recommended for a 2‐ or 5‐d follow‐up visit. Children who did not return were visited and assessed at home. Results: Only 87 children (56.9%) timely returned for follow‐up: 70 had improved, eight presented the same health conditions, five were worse and four had a new problem. The main reasons given for not returning for follow‐up were: the child had improved (35.1%) and other family priorities (47.4%). Home visits showed that, although most children had improved (n=49), some had a new health problem and one child was sick enough to be referred. Prescription of antibiotics was associated with increased probability of returning for a follow‐up visit (RR =1.64 [1.22–2.20], p=0.001).

Conclusion: Adherence to follow‐up was just over 50%, mostly because the condition had already resolved, but some children were still sick and needed intervention. Training on counselling on the recognition of danger signs and when to return for a follow‐up visit must be reinforced.
Vaccination coverage among adolescents in certain provinces of Greece
Authors: Bitsori Maria , Ntokos Michail , Kontarakis Nikolaos , Sianava Ourania , Ntouros Thomas , Galanakis Emmanouil
Published: August 2010

Aim: To estimate the vaccination coverage in a sample of adolescents in Greece. Methods: Vaccination status was estimated in 483 adolescents aged 15–19 y in four prefectures. The criteria for full vaccination were based on the recommendations of the Greek National Vaccination Schedule. Results: The participation rate in the study was 78.7% (380/483 adolescents). The rates of full vaccination were 94.2% for poliomyelitis, 78.4% for hepatitis B, 77.4% for BCG, 65.0% for tetanus and 54.4% for diphtheria. The rates of full vaccination for measles, rubella and mumps were 65.0%, 57.6%, and 56.0%, respectively. For pertussis, the full vaccination rate was only 36.0%, and 7.1% of the study population was totally unvaccinated. The most missed dose for all vaccines was the final booster dose, which is usually administered in older children or adolescents.

Conclusion: Adolescent vaccination coverage was not satisfactory in this study, mainly due to non‐compliance to the final booster dose. Completion of missing vaccines at this age represents the last opportunity for massive intervention and would be of essential value for individual and community protection against common preventable diseases.
Hypertrophic osteoarthropathy in two children with cholestatic hepatic disease
Authors: Katsicas M , Ciocca M , Rosanova M , Russo Ricardo AG
Published: August 2010

Aim: To describe two children with hypertrophic osteoarthropathy associated with cholestatic hepatic disease. Both patients suffered from chronic progressive cholestatic liver disease and developed digital clubbing, polyarthritis and periosteal reaction. In one of them, clinical and radiological features normalized after liver transplant.

Conclusion: Hepatic hypertrophic osteoarthropathy is a rare disabling condition that responds poorly to conservative management, while liver transplantation appears to be the only effective therapeutic intervention.
Purpura fulminans as a sequel to erythema nodosum in a child with homozygous Leiden mutation and acquired protein S deficiency
Authors: Foyn Bruun Cathrine , Langbakk Bodil , Eriksson Steigen Sonja
Published: August 2010

A 6‐y‐old boy presented with generalized, bruise‐like swelling of both legs. Three weeks later, he developed purpura fulminans in one of the affected feet. Histology of the leg swelling was in accordance with erythema nodosum. The boy proved to be homozygous for the Factor V Leiden mutation and to have acquired protein S deficiency. He recovered, with partial loss of two toes.

Conclusion: In contrast to what is often stated, erythema nodosum is not always a benign condition. On the basis of this report, we suggest that if extensive erythema nodosum develops in an individual without any known thrombophilic disorder, investigations with respect to the latter should be performed.
Informed consent and hypoplastic left heart syndrome
Authors: Byrne Paul J. , Murphy Aisling
Published: August 2010

We present an ethical analysis from the perspective of shared decision‐making and informed consent of a change in clinical management of infants born with hypoplastic left heart syndrome (HLHS). We reported a change in treatment of HLHS at the University of Alberta away from comfort care to life‐saving surgery (LST) between 1987 and 1998. In a second review (1996–2001), 49/62 infants received LST, with 81% survival from the NICU and 58% at 35 mo. Eleven infants died preoperatively of non‐cardiac conditions and two received elective comfort care. Sixteen infants had 18‐mo Bayley Mental Development Index, mean score 84±19, but five scored <70. Although we continue to present the comfort care option to parents, since 2001 LST use for HLHS at our center is almost universal despite serious complications.

Conclusion: We conclude that these findings are inconsistent with an open, shared decision‐making model of informed consent and we suggest that comfort care should remain an ethically valid choice until the rate of serious long‐term complications of LST decreases.
Macronutrient and energy contents of human milk fractions during the first six months of lactation
Authors: Saarela Timo , Kokkonen Jorma , Koivisto Maila
Published: August 2010

Aim: To study the macronutrient and energy contents of human milk fractions during the first 6 mo of lactation. Study design: A total of 483 milk samples, including 52 pairs of fore‐ and hindmilk samples from 20 mothers, 253 samples from 53 donor mothers and 126 samples from 36 mothers of preterm infants, were collected longitudinally, starting at 1 wk postpartum and continuing monthly up to 6 mo. Protein, lactose and fat contents were measured and energy density estimated. Results: The protein content was significantly lower in fore‐ and hindmilk than in donor or preterm milk during the first months of lactation. In donor and preterm milk, the protein content declined consistently from 2.0 g/100 ml at 1 wk to half of that at 6 mo, and a similar trend was observed in fore‐ and hindmilk. Lactose content showed no significant changes between the groups or in the course of lactation. The fat content was highest in hindmilk, being approximately two‐ to threefold that of foremilk. Accordingly, hindmilk included 25–35 kcal/100 ml more energy on average than foremilk.

Conclusions: The fat content of human milk increases in relation to breast emptying, while the other macronutritients of milk show only slight changes. When enteral feeding with high‐energy human milk is preferred, as in the case of very preterm infants, hind milk, with its higher fat content, would be a natural choice.
Children with early refusal to eat: Follow‐up in adolescence
Authors: Rydell Ann‐Margret , Dahl Margareta
Published: August 2010

Aim: To describe the adolescent outcome of infant refusal to eat (RTE) and to investigate early predictors of adolescent outcomes. Methods: 19 of 25 children with RTE and 35 of 42 controls were assessed at age 16. The participants rated eating attitudes and self‐perceptions with a Swedish version of the Children's Eating Attitudes Test (ChEAT) and a Swedish self‐perception measure. Weight and height were assessed through self‐reports, and body mass index (BMI) was computed. Child and family variables measured from infancy through age 4 were used as predictors. Results: RTE and controls did not differ with regard to disturbed eating attitudes, BMI or self‐perceptions. There were no relations between early predictors and adolescent disturbed eating for the whole sample, but breastfeeding problems and social adversity in the early years predicted negative self‐perceptions, and weight at 4 y predicted adolescent BMI. For the RTE group, low birthweight predicted higher levels of disturbed eating attitudes and less positive self‐perceptions. For the control group, social adversity predicted high BMI.

Conclusion: RTE does not seem to constitute a risk factor for adolescent disturbed eating. Further, there may be different risk factors for adolescent disturbed eating for children with and without RTE.
Behavioural effects of phenylalanine‐free amino acid tablet supplementation in intellectually disabled adults with untreated phenylketonuria
Authors: Kalkanoğlu H. Serap , Ahring Kirsten K. , Sertkaya Durdu , Birk Møller Lisbeth , Romstad Anne , Mikkelsen Ingrid , Guldberg Per , Lou Hans C. , Güttler Flemming
Published: August 2010

Aim: To evaluate the effects of phenylalanine (Phe)‐free essential amino acid (AA) tablets enriched in tyrosine and tryptophan on the performance of intellectually disabled adult patients with untreated phenylketonuria (PKU). Methods: Phe‐free AA tablets and placebo tablets were administered to 19 untreated PKU subjects on a normal diet for 6 mo in a prospective double‐blinded crossover study. The adaptive behaviour of the patients was tested prior to the study and at 6 and 12 mo after the start, using a simplified version of the Vineland Adaptive Behaviour Scale. For each sub‐domain, the patients were rated either “0” (for poor performance) or “1” (for good performance). Neurological signs and symptoms and specific behavioural characteristics were recorded monthly by caretakers. Every 6 mo, neurological examination of the patients was performed, and the caretakers were interviewed. The statistical significance of the results was tested by means of the Fisher's exact and Wilcoxon tests. Results: The most significant changes were an improved concentration and the development of a meaningful smile, which were observed in 44% and 43% of the patients on AA tablet treatment, respectively, but not patients on placebo. Other important but less significant changes included increased awareness of external stimuli (63%) and less self‐injury (43%), and 40% were smiling and laughing occasionally. The mean overall rating increased from an initial value of 6.3 to 10.1 in patients when on AA tablet treatment (p=0.002), and to 7.0 in patients when on placebo (p=0.068). The difference between active AA treatment and placebo was statistically significant (p=0.027).

Conclusions: This pilot study suggests that Phe‐free AA tablets enriched in tyrosine and tryptophan may improve the quality of life in some intellectually disabled adults with untreated PKU.
Autonomic nervous system functions in children with breath‐holding spells and effects of iron deficiency
Authors: Kolkiran Abdülkerim , Tutar Ercan , Atalay Semra , Deda Gülhis , Cin Şükrü
Published: August 2010

Aim: To analyse the activity of the autonomic nervous system during breath‐holding spells, we assessed the ECG changes, including ventricular repolarization parameters before and during the spell. We also analysed the effects of iron deficiency on these ECG parameters. Methods: The study group consisted of 37 children with breath‐holding spells (30 cyanotic, 7 pallid) (mean age±SD: 12.9±10.8 mo). Twenty‐six healthy children (mean age±SD: 14.4±8.6 mo) served as a control group. All patients and controls had standard 12‐lead simultaneous surface ECG. All patients had ECG recordings during at least one severe breath‐holding spell obtained by “event recorder”. Traces obtained by “event recorder” were analysed in terms of mean heart rate and the frequency and duration of asystole during the spell. Results: Respiratory sinus arrhythmia on standard ECGs and asystole frequency during spells were higher in patients with pallid breath‐holding spells. Patients with iron deficiency had a lower frequency of respiratory sinus arrhythmia and prolonged asystole time during the spell. There was no difference in terms of ventricular repolarization parameters (QT/QTc intervals and QT/QTc dispersions) between patients and controls and between patient subgroups (cyanotic versus pallid).

Conclusion: These results confirmed the presence of autonomic dysregulation in children with breath‐holding spells. Iron deficiency may have an impact on this autonomic dysregulation. Ventricular repolarization was unaffected in patients with breath‐holding spells.
Improved final height with long‐term growth hormone treatment in Noonan syndrome
Authors: Osio Deborah , Dahlgren Jovanna , Wikland Kerstin Albertsson , Westphal Otto
Published: August 2010

Aim: To assess whether children with Noonan syndrome on long‐term growth hormone (GH) therapy improve their final height to near mid‐parental height. Methods: Twenty‐five prepubertal children (13 girls) with Noonan syndrome (NS) were studied. A single clinician made the diagnosis based on clinical criteria. GH treatment started at an age ranging from 3.1 to 13.8 y and was continued for at least 2 y. Improvement or “gain” in final height (FH) was defined as either the difference between adult height SD scores (SDS) and pre‐treatment height SDS (the childhood component of the Swedish reference) or height SDS compared to the Noonan reference. Results: Ten children received a GH dose of 33 μg/kg/d (mean age at start 7.7±2.1 y, mean age at stop 17.6±1.7 y) and 15 received a dose of 66 μg/kg/d (mean age at start 8.6±3.3 y, mean age at stop 18.4±2.1 y). Eighteen out of 25 patients reached FH. A substantial improvement in FH of 1.7 SDS, equivalent to 10.4 cm compared to pre‐treatment height, was observed. No significant difference was seen between the two GH doses. Females gained a mean height of 9.8 cm and males 1–13 cm (FH 174.5±7.8 cm vs mean adult height of 162.5±5.4 cm for males with NS) at final height. Moreover, 60% reached a mid‐parental height of±1 SD.

Conclusion: GH treatment improves final height in patients with Noonan syndrome, with a mean gain of 1.7 SDS. The prepubertal height gain is maintained to final height and the children achieve a height close to their mid‐parental height.
Early post‐convulsive prolongation of QT time in children
Authors: Kändler Liane , Fiedler Andreas , Scheer Katrin , Wild Florentine , Frick Ulrich , Schneider Peter
Published: August 2010

Aim:An important differential diagnosis of seizures in childhood is the long QT syndrome. Childhood epilepsy occurs about 400 times more often than long QT syndrome. We had observed children with slight post‐convulsive prolongation of QT time more often than the reported incidence of long QT syndrome. We therefore conducted a prospective study to define the characteristics of post‐convulsive prolongation of QT time in children.Methods:We investigated 30 consecutive infants and children (3 mo to 14 y) within 2 h after seizures. A follow‐up ECG was obtained 1–9 d later. We also obtained ECGs from 30 healthy age‐ and gender‐matched controls. We calculated the QT interval corrected for heart rate (QTc) by Bazett's formula in leads II, V5, V6, QT dispersion and the number of notched T waves.Results:We found a QTc interval of more than 440 ms in one or more leads in the first ECG in seven of 30 infants and children compared to 1 of 30 in the follow‐up ECG (p=0.0003) and two of 30 in the healthy controls (p=0.14). Average QTc was higher for all leads in the first ECG. This was statistically significant in leads II (414 vs 402 ms,p=0.008), V5 (416 vs 404 ms,p=0.002) and V6 (415 vs 399 ms,p=0.001). Compared to healthy controls, QT dispersion was slightly larger in the early post‐convulsive ECG (36 vs 31 ms,p=0.03). Notched T waves occurred more frequently in the early compared to the late post‐convulsive ECGs (p=0.009).

Conclusion:Slight to moderate post‐convulsive prolongation of the QT interval is not rare but transient in paediatric patients.
Use of supplementary equipment for resuscitation of newborn infants at tertiary perinatal centres in Australia and New Zealand
Authors: O'donnell Colm P. F. , Davis Peter G. , Morley Colin J.
Published: August 2010

Aim: Neonatal resuscitation is a common and important intervention. International consensus statements advise how newborns should be resuscitated and suggest equipment to be used. Use of equipment not specifically recommended in these guidelines has been advocated. We wished to determine how widely this supplementary equipment is used in a geographically defined region. Methods: Each of the 25 tertiary perinatal centres with on‐site deliveries in Australia and New Zealand was surveyed. The questionnaire asked about the use of the following items during delivery room resuscitation: pulse oximetry, exhaled carbon dioxide detection, polyethylene wrapping, oxygen blenders, laryngeal mask and oropharyngeal airways. Results: Data were obtained from all centres. Pulse oximetry is used at 12 (48%) centres. Exhaled CO2detection is used to confirm endotracheal tube placement at three (12%) of the centres. Polyethylene wrapping is used to prevent heat loss in very‐low‐birthweight infants at delivery at 11 (44%) centres. Oxygen blenders are used to modify the amount of oxygen delivered at nine (36%) centres. Laryngeal mask airways are infrequently used at two (8%) centres. Oropharyngeal airways are infrequently used at five (20%) centres.

Conclusion: There is considerable variation in the equipment and techniques used to resuscitate newly born infants. Use of equipment not specifically recommended in international consensus statements is widespread. These are potentially effective tools to improve resuscitation. The evidence supporting their use is, however, limited. Urgent evaluation of their efficacy and safety is required before even more widespread use occurs.
Outcome in neonates with congenital heart disease referred for respiratory extracorporeal membrane oxygenation
Authors: Brown Kate L. , Miles Fiona , Sullivan Ian D. , Hoskote Aparna , Verhulst Linda , Ridout Deborah A. , Goldman Allan P.
Published: August 2010

Aim: To evaluate the proportion of neonates referred for extracorporeal membrane oxygenation (ECMO) support in the modern era of advanced conventional treatments for respiratory failure who actually had congenital heart disease (CHD), and to assess the impact of this diagnostic route on patient condition and outcome. Methods: A retrospective case‐note review of neonatal ECMO and cardiac admissions to a single, tertiary ECMO and cardiac intensive care unit (ICU) between March 1999 and February 2002. Results: 287 symptomatic neonates presented to the ICU with previously undiagnosed cardiac or respiratory disease. Eighty‐two with presumed respiratory failure were referred for ECMO, and 205 with suspected CHD were referred for cardiac evaluation. Eight (10%) ECMO referrals, all with presumed persistent pulmonary hypertension of the newborn (PPHN), were found to have CHD (transposition: 3; total anomalous pulmonary venous connection: 3; left heart obstructive lesions: 2). Mortality in this group was 50%, compared with 11% for correctly identified CHD patients (odds ratio 8.2, 95% CI 1.92, 35.4, p<0.01). For all neonates with CHD, the risk of death was increased by the presence of cardiovascular collapse and end‐organ dysfunction at presentation to the ICU (p<0.01 for both).

Conclusion: Neonates with CHD may present as severe “PPHN” via the ECMO service. Poor outcome in these patients relates to the high incidence of cardiovascular collapse and end‐organ dysfunction. Early echocardiography is recommended for neonates with presumed PPHN. Neonatal ECMO support should be based in centres with cardiac surgical services.
Mothers' experiences of child health clinic services in Sweden
Authors: Örtenstrand Annica , Waldenström Ulla
Published: August 2010

Aim: To investigate women's experiences of child health clinic (CHC) care and risk factors for being dissatisfied. Experiences of specific aspects of care were further explored in subgroups of women who were not generally satisfied. Methods: All Swedish‐speaking women admitted to any of the approximately 600 antenatal clinics in Sweden during 3 wk evenly spread over 1 y in 1999 and 2000 were invited to participate in the study. Altogether, 3113 women agreed to participate. Data were collected by questionnaires: in early pregnancy, 2 mo and 1 y postpartum, and from the Swedish Medical Birth Register. For the purpose of this study, data from the 2415 women who answered the question used as the principal outcome in this study, i.e. overall satisfaction with CHC care, were analysed. Results: Psychological factors, such as maternal depressive symptoms and worry about caring for the newborn, and serious infant feeding problems were predictors of less satisfied or mixed feelings about CHC care. About one in three women were dissatisfied with the attention paid to their own needs, and a similar proportion said information about vaccinations was insufficient. Of the four subgroups—mothers whose babies had feeding problems and mothers with depressive symptoms at 2 mo, 1 y, and on both occasions—the latter group was the least satisfied with the nurse and the time allocated to various issues.

Conclusions: Swedish mothers appear to be satisfied with the attention given to their infants at CHCs, but many feel that their own needs as new mothers are neglected. This study supports current development towards screening for maternal depression at CHCs.
Socio‐economic determinants, maternal smoking and coffee consumption, and exclusive breastfeeding in 10 205 children
Authors: Ludvigsson Jonas F. , Ludvigsson Johnny
Published: August 2010

Aim:To examine socio‐economic factors, smoking, coffee consumption and exclusive breastfeeding duration.Methods:This study was part of a prospective cohort study of children born between 1 October 1997 and 1 October 1999 (the All Babies in Southeast Sweden (ABIS) study). Eleven socio‐economic characteristics (parental employment, civil status, whether parents were born in Sweden, parental education, residence at birth and during child's first year, crowded living), maternal smoking, coffee consumption, infant sex, siblings, parental age, and maternal alcohol consumption during pregnancy were analysed using logistic regression and Cox's proportional hazards method. All data were obtained through questionnaires distributed at infant birth and at 1 y of age. Exclusive breastfeeding duration <4 mo and actual breastfeeding duration were our main outcome measures.Results:Out of 10&!hairsp;205 infants, 2&!hairsp;206 (21.6%) were exclusively breastfed for less than 4 mo (“short exclusive breastfeeding”; SEBF). Backward stepwise regression analysis identified the following risk factors for SEBF: maternal smoking (95% confidence interval for adjusted odds ratio, 95% CI AOR 2.00–2.82), low maternal education (95% CI AOR 1.45–2.19), maternal employment less than 3 mo during pregnancy (95% CI AOR 1.17–1.54), paternal age 29 y (95% CI AOR 1.14–1.47), maternal age 29 y (95% CI AOR 1.08–1.39) and low paternal education (95% CI AOR 1.08–1.48). The odds ratio for SEBF increased with the number of cigarettes smoked. Coffee consumption was not associated with duration of exclusive breastfeeding.

Conclusion:This study indicates that socio‐economic factors and smoking may be of importance to the risk of breastfeeding exclusively for less than 4 mo, while coffee consumption is not.
Gender affects self‐evaluation in children with cystic fibrosis and their healthy siblings
Authors: Wennström Inga‐lill , Berg Ulla , Kornfält Ragnhild , Rydén Olof
Published: August 2010

Aim: To determine whether self‐esteem among children with cystic fibrosis (CF) and their healthy siblings differs from that of a healthy reference group and whether there are differences within and between sibling pairs. Methods: All Swedish CF children 6–14 y old with a healthy sibling in the same age range (n=65) were invited to participate, 55 sibling pairs and their parents taking part in the study. Five aspects of the children's self‐concept—physical characteristics, skills and talents, mental well‐being, relations to parents and family, and relations to others—were assessed by the “I think I am” self‐evaluation questionnaire. Severity of illness was assessed by means of the Shwachman Clinical Evaluation System. Results: Whereas self‐evaluation did not differ between groups at a general level, healthy girls as well as those with CF scored lower than girls in the reference group on the “mental well‐being” and “relations to parents and family” subscales. Comparison of gender combinations (sick girl/healthy boy, sick girl/healthy girl, sick boy/healthy boy, sick boy/healthy girl) suggested that girls pay a cost of a lesser sense of psychological well‐being and feelings of inadequacy in relation to their parents and family. The Shwachman score of the sick child was not related to the level of self‐esteem.

Conclusion: When CF is present among siblings, girls seem to carry more of the family pain than boys, a finding that calls for an increased awareness of the girls' situation by members of care teams.
Ages and Stages Questionnaire used to measure cognitive deficit in children born extremely preterm
Authors: Klamer Anja , Lando Ane , Pinborg Anja , Greisen Gorm
Published: August 2010

Aim: To validate the Ages and Stages Questionnaire (ASQ) and to measure average cognitive deficit in children born extremely preterm. Methods: Parents of 30 term children aged 36–42 mo completed the ASQ and the children underwent the Wechsler Preschool and Primary Scales of Intelligence—Revised. In a second study, the ASQ was obtained in 22 children born extremely preterm and 19 term children at the age of 35–44 mo. Results: The overall ASQ score correlated significantly with IQ (p=0.007). The children born extremely preterm had an ASQ score of −1.06 SD below the score of the term children (p=0.048).

Conclusion: The ASQ identified a developmental deficit of the expected magnitude.
Neurodevelopmental outcome and haematological course of a long‐time survivor with homozygous alpha‐thalassaemia: Case report and review of the literature
Authors: Lücke Thomas , Pfister Stefan , Dürken Matthias
Published: August 2010

Aim: Homozygous α‐thalassaemia, also called haemoglobin (Hb) Bart's hydrops fetalis, has been thought to be a lethal condition. Due to prenatal diagnosis and intrauterine blood transfusions, a few patients with Hb Bart's hydrops fetalis have survived. This fact raises the urgent questions of clinical management and appropriate follow‐up of these patients, both of which are addressed in this article. Methods: We report on a 6.5‐y‐old patient with homozygous α‐thalassaemia and review the literature of 13 other survivors published to date. Transfusion requirements were evaluated and the rate of liver iron accumulation was assessed by biomagnetic liver susceptometry before and after institution of iron‐chelating therapy. Psychometric evaluation was carried out using Munich's Functional Development Test, the Columbia Mental Maturity Scale, the Kaufman Assessment Battery for Children, and the Peabody Picture Vocabulary Test. Results: Our patient had significant delay of psychomotor development. Psychometric evaluation at the age of 5 y revealed an IQ of 85 and an intellectual level of a 4‐y‐old child. Early tissue iron overload was seen, but a negative iron balance was achieved after institution of desferrioxamine treatment at dosages used for β‐thalassaemia.

Conclusion: Homozygous α‐thalassaemia should no longer be regarded as a lethal condition. Early intervention during pregnancy and careful haematological as well as neuropsychological follow‐up was able to provide long‐term survival and good life quality in our patient.
The right ventricle in Fabry disease
Authors: Kampmann C , Baehner FA , Whybra C , Bajbouj M , Baron K , Knuf M , Wiethoff CM , Trübel H , Beck M
Published: August 2010

Aim: Left ventricular (LV) hypertrophy is a common feature in Fabry disease‐related progressive infiltrative hypertrophic cardiomyopathy and affects both men and women, but at different ages. To date, however, little is known about the role of right ventricular (RV) function in Fabry disease. Therefore, this study aimed to investigate the extent of RV involvement in patients with Fabry disease. Methods: Echocardiographic examination of the right and left ventricle was carried out in 129 patients (80 women and 49 men) with Fabry disease. Results: RV hypertrophy was present in 46 patients (35.7%). Of these patients, 13 showed signs of severely depressed right systolic function (tricuspid annulus movement <10 mm and a prolonged RV pre‐ejection period/pulmonary ejection time ratio) and six patients showed additional severe depression of parameters of diastolic function (pseudo‐normal or restrictive RV filling patterns). Those patients with RV hypertrophy and severely compromised systolic and diastolic function had the highest LV masses (92±11.7 g/m2.7).

Conclusion: RV involvement is common in Fabry disease and ultimately progresses to severe systolic and diastolic RV dysfunction. These findings might explain why patients with preserved LV function can develop clinical features such as reduced exercise capacity, organomegaly and lymphoedema.
Vascular complications of Fabry disease: enzyme replacement and other therapies
Authors: Hughes DA , Mehta AB
Published: August 2010

Fabry disease is an X‐linked glycosphingolipid storage disorder resulting from deficiency of α‐galactosidase A. Storage of globotriaosylceramide ultimately results in multiorgan pathology, including cerebrovascular, cardiovascular and renal disease. Vascular involvement is evident throughout the body but the mechanisms by which storage on a cellular level leads to end‐organ pathology are unknown. Here the evidence for abnormal blood flow, vessel architecture and endothelial function will be reviewed and possible models of vascular pathology discussed. The effects of reversal of storage within vessels by enzyme replacement therapy (ERT) and the possibilities for intervention with additional agents will be considered.

Conclusion: The pathology of Fabry disease has an important vascular component, although the underlying pathophysiology is unclear. Preliminary evidence suggests that ERT may have beneficial effects on the vascular component of this multisystem disease.
Clinical evaluation of biomarkers in Gaucher disease
Authors: Deegan PB , Cox TM
Published: August 2010

Novel or candidate biomarkers require thorough evaluation to establish their utility in a clinical setting. This paper describes an evaluation of several established enzyme markers of Gaucher disease and a newly‐described chemokine, pulmonary and activation‐regulated chemokine (PARC). The ability of the biomarkers to rank patients with Gaucher disease in order of disease severity and organ bulk, and to reflect changes in key clinical parameters in response to enzyme replacement therapy were evaluated. PARC concentrations were found to be reliably correlated with visceral disease and with key clinical responses to enzyme replacement in an unbiased manner. Unlike chitotriosidase and serum angiotensin‐converting enzyme activity, genetic variation in serum PARC did not appear to influence its utility as a biomarker.

Conclusion: For each new candidate biomarker of lysosomal storage diseases, a similar clinical evaluation will be required, though the approach will need to be modified according to the clinical features and natural history of each disorder.
Substrate reduction therapy for lysosomal storage diseases
Authors: Cox T M
Published: August 2010

The treatment of disordered lipoprotein metabolism with the statin class of drugs is one of the most striking successes in the field of applied medical science: here the use of selective inhibitors of the first committed step of cholesterol biosynthesis, in a complex and highly regulated pathway, leads to improved outcome from a common lipid storage disease that is a blight on whole populations – atherosclerosis. By the same token, substrate reduction is an emerging therapeutic strategy for the arcane field of the lysosomal storage diseases (LSDs). Reduced biosynthesis of glucosylceramide is postulated to allow correction of the imbalance between formation and breakdown of glycosphingolipids; the therapeutic effect of substrate reduction depends upon the presence of residual hydrolytic activity towards those accumulated glycosphingolipid substrates derived from glucosylceramide. First pioneered in the laboratory by Norman Radin, this approach has now been introduced into the clinic: based on the ability to inhibit uridine diphosphate glucosylceramide transferase, the semi‐selective iminosugar, N‐butyldeoxynojirimycin, is licensed for the treatment of type 1 Gaucher disease.

Conclusion: Inhibition of substrate formation has wide application in the treatment of LSDs. Decreased glucosylceramide biosynthesis has therapeutic potential in glycosphingolipidoses other than Gaucher disease, and offers promise in several neurodegenerative storage disorders that are currently beyond the reach of other procedures. The results of ongoing clinical trials of miglustat in type 3 Gaucher disease, Niemann–Pick disease type C and GM2 gangliosidosis are eagerly awaited.
Genotype and phenotype in Fabry disease: analysis of the Fabry Outcome Survey
Authors: Schaefer E , Mehta A , Gal A
Published: August 2010

Aim: Mutations of the gene (GLA) encoding α‐galactosidase A are implicated in Fabry disease, a progressive, X‐chromosomal inherited lysosomal storage disorder. FOS – the Fabry Outcome Survey – was established as a long‐term surveillance study to describe the natural course of Fabry disease and its response to enzyme replacement therapy in a large cohort of European patients. Clinical phenotype, age of onset and course of Fabry disease are very variable, even within the same family, which makes it difficult to define a genotype–phenotype relationship by analysing individual patients. The FOS database contains detailed medical information on a large cohort of patients and thus has the potential to provide important information to address this question. Methods: At the time of analysis, information on 545 patients belonging to 157 families from nine European countries had been entered into the FOS database. A GLA mutation has been reported in 365 individuals (65% and 68% of all males and females, respectively) in FOS. These data were used to analyse the relationship between genotype and phenotype in Fabry disease. Results: A highly significant positive correlation was found between the age at entry into FOS and the FOS Severity Index in male patients with GLA missense mutations (p<0.001) as well as in those carrying other types of mutations (p<0.001). A positive correlation was also found between the age at entry into FOS and the number of affected organs in male patients with missense mutations, irrespective of whether the change in the amino acid side chain predicted in the α‐galactosidase A protein was classified as a conservative or non‐conservative change.

Conclusion: The data presented here suggest that there is a correlation between genotype and clinical severity.
Dietitians and exercise professionals in a childhood obesity treatment team
Authors: Nowicka Paulina
Published: August 2010

There has been a remarkable increase in the prevalence of childhood obesity in most countries in recent years, which indicates that modern lifestyle is the triggering factor for genetic susceptibility. This report focuses on the two main environmental factors, nutrition and physical activity, that could influence paediatric obesity development, and how health professionals can address these aspects in the management of childhood obesity in a multidisciplinary treatment team. First, the role of a nutrition expert in the multidisciplinary obesity team is discussed and then the importance of physical activity in the treatment of paediatric obesity. The part on nutrition highlights some interesting areas in this field, namely glycaemic index, high‐protein diet, fast foods, portion sizes and soft‐drink consumption. Dietary treatment in childhood obesity should be combined with changes in physical activity to promote long‐term weight loss. Research on the physical activity of children and adolescents indicates some significant changes over the last decades, which are also reviewed. Factors such as sports club participation and television viewing are discussed. The appropriate physical activity level and effective physical activity programmes are also presented. Physical activity can be promoted in childhood obesity treatment in many ways. Practical advice regarding physical activity programme and the role of exercise professionals in childhood obesity treatment team is given.

Conclusion: For successful obesity management, the child should be assessed and treated by a multidisciplinary team, including a physician, dietitian, exercise expert, nurse and behavioural therapist.
Appetite regulation and energy balance
Authors: Erlanson‐Albertsson Charlotte
Published: August 2010

The decision to begin eating or to stop eating is a complex process. Hunger is primarily driven by hunger signals, like ghrelin and neuropeptide Y, originating from the gastrointestinal tract and from the hypothalamus. The hunger signals stimulate the seeking of food and the eating, being activating for the body and mind. Thirty minutes after the start of eating, satiety signals arise from the intestinal tract and, in between meals, from the adipose tissue and liver. Satiety signals are sedative and arrest the processing of food in the intestine, hence leading to termination of eating. One problem with overeating today is the ready access to palatable food, such as sucrose and fat. The palatable food works by weakening the satiety signals and activating the hunger signals. The reward system with endogenous opiates may also be activated.

Conclusions: Food and drinks rich in sucrose and fat should be given in a restricted way to children, since there is no biological control feedback to regulate the intake of such products.
Family therapy treatment: Working with obese children and their families with small steps and realistic goals
Authors: Peterson Ywonne
Published: August 2010

Childhood obesity treatment can be discussed from several points of view, and there are many forms of treatment. Solution‐focused brief therapy (SFBT) and systemic family therapy can be useful in a wide range of contexts and settings such as social care, education and healthcare. They can also be used wherever practitioners sometimes feel that they have very little impact on the patient and where the patient seems to be resistant to acknowledging his/her problem. Health professionals need to assist by starting to explain main goals and medical information in terms of a single, small, concrete and important goal, described as the beginning of a new behaviour, not as the end of something. This report focuses on some useful tools and methods taken from casework examples from multidisciplinary obesity team meetings with more than 300 families during a 3‐y project approximately between 2002 and 2003 at the Childhood Obesity Unit at University Hospital, Malmö. Other casework examples are taken from supervision and training professionals who are currently working with or are going to work with childhood obesity using a solution‐focused model. The main aim of this report is to discuss and think about the difference between problem‐solving and solution‐building interview questions when it comes to treatment regarding how best to help children and parents with serious obesity health problems.

Conclusion: There is a great need for treatment models and the prevention of childhood obesity now and in future, which presents an interesting and urgent challenge for open‐minded thinking and new fields of research.
Introduction to medical family therapy
Authors: Wirtberg Ingegerd
Published: August 2010

The onset of illness and/or disability in children may also create difficulties at psychosocial levels – for the child, the family, her network and even in relations between them and the medical team. Medical family therapy, coupled with salutogenic theory and Marte meo offers specific ways of working with such difficulties so that the family and the medical team can work together in a mutually supportive manner.
Reproducing the bifidogenic effect of human milk in formula‐fed infants: Why and how?
Authors: Moro Guido E , Arslanoglu Sertac
Published: August 2010

Awareness of the key role of the intestinal microflora in the generation of the immunophysiological regulation and in the defence against pathogenic agents has attracted our interest in ways of manipulating the microbiota to improve health. Dietary modulation of the intestinal microflora is today one of the main topics of interest in the nutritional sciences. Performing this modulation in the neonatal or early infancy period, when immunological programming takes place, is a relatively new concept. Fructo‐oligosaccharides (FOS) and galacto‐oligosaccharides (GOS) are prebiotics whose bifidogenic activity has been proven in adults. However, only recently have they been combined in infant formulas to reproduce the prebiotic effect of human milk oligosaccharides. In two consecutive trials, it has been demonstrated that supplementation of infant formulas with a mixture of GOS and FOS modified the fecal flora of term and preterm infants, stimulating the growth of Bifidobacteria. In the trial with term infants, the bifidogenic effect of the prebiotic mixture was dose dependent and there was also a significant increase in the number of Lactobacilli in the supplemented group. These findings offer a promising horizon for the early prevention of allergy and infections in infants.
Dietary prebiotic oligosaccharides are detectable in the faeces of formula‐fed infants
Authors: Moro Guido E , Stahl Bernd , Fanaro Silvia , Jelinek Jürgen , Boehm Günther , Coppa Giovanni V
Published: August 2010

Human milk oligosaccharides are not digested during intestinal passage and can be detected in stools. In this study it was investigated whether a prebiotic mixture of low‐molecular‐weight galacto‐oligosaccharides (GOS) and high‐molecular‐weight fructo‐oligosaccharides (FOS) can be detected in stool samples of formula‐fed infants. The test formula was supplemented with 0.8 g/dl oligosaccharides (GOS+FOS). In the control formula, maltodextrins were used as placebo. Fecal flora was assessed at the beginning (day 1) and at the end of a 28‐d feeding period (day 2). At day 2 the content of galacto‐ and fructo‐oligosaccharides in the stool samples were measured. On study day 1, the number of bifidobacteria was not different among the groups (supplemented group: 7.7 (6.2) CFU/g; placebo group: 8.0 (6.0) CFU/g). At the end of the 28‐d feeding period, the number of bifidobacteria was significantly higher in the group fed the supplemented formula when compared to placebo (supplemented group: 9.8 (0.7) CFU/g stool; placebo group: 7.1 (4.7) CFU/g stool; p<0.001). In all infants fed the supplemented formula, GOS and FOS could be identified in the stool samples. That was not the case in infants fed the non‐supplemented formula.

Conclusion: The present data confirm the bifidogenicity of oligosaccharides and indicate that dietary galacto‐oligosaccharides and long chain fructo‐oligosaccharides remain during the whole passage in the lumen of the gastrointestinal tract, similarly to human milk oligosaccharides.
Effects of specific lactic acid bacteria on the intestinal permeability to macromolecules and the inflammatory condition
Authors: Heyman Martine , Terpend Kathleen , Ménard Sandrine
Published: August 2010

Non‐live probiotic bacteria and their fermentation products can be used in milk‐based formula intended for healthy infants. The effects of a milk formula fermented with Bifidobacterium breve and Streptococcus thermophilus and heated/dehydrated to inactivate the micro‐organisms have been reported over the last few years to decrease the intestinal permeability to macromolecules in experimental animals in vivo and more recently to down‐regulate inflammatory condition in vitro. Feeding guinea‐pigs with such dehydrated fermented milk reinforced the intestinal barrier resistance to food proteins (HRP, β‐lactoglobulin). In addition, the products secreted by bacteria were capable of inhibiting the lipopolysaccharide (LPS)‐induced TNF‐α secretion by human peripheral mononuclear blood cells. The active secretion products were resistant to digestive enzymes and their anti‐inflammatory properties were preserved after transepithelial transport across the filter‐grown intestinal epithelial cell line, especially in inflammatory conditions. The binding of LPS to monocytes as well as NFκB nuclear translocation leading to pro‐inflammatory cytokine transcription were inhibited by bacteria‐culture supernatants.

Conclusion:
B. breve and S. thermophilus used as non‐live micro‐organisms in fermented infant formula seem to induce a reduction in macromolecular absorption and release metabolites exerting an anti‐TNF‐α effect, which persists after intestinal transport. Thus, specific lactic acid bacteria and their metabolites seem to affect positively the intestinal function.