bluuebunny/crossref_metadata_2025 huggingface dataset:
No indications of increased quiet sleep in infants receiving care based on the Newborn Individualized Developmental Care and Assessment Program (NIDCAP)
Authors: Westrup B , Hellström‐Westas L , Stjernqvist K , Lagercrantz H
Published: August 2010

It has been proposed that the developmentally supportive care of very‐low‐birthweight (VLBW) infants provided by the Newborn Individualized Developmental Care and Assessment Program (NIDCAP) can improve the infants' opportunities for rest and sleep. The aim of the present study was to determine whether quiet sleep (QS) in VLBW infants is affected by NIDCAP care. Twentytwo infants with a gestational age of <32 wk at birth randomly received either NIDCAP (n= 11) or conventional care (n= 11). These two groups were comparable (mean (SD)) with respect to birthweight (1021 (240) vs 913 (362) g, respectively) and gestational age (27.1 (1.7) vs 26.4 (1.8) wk). The infants in the NIDCAP group were cared for in a separate room by a group of specially trained nurses and subjected to weekly NIDCAP observations until they reached a postconceptional age (PCA) of 36 wk. Quiet sleep (QS) was assessed from 24‐h amplitude‐integrated EEGs recorded at 32 and 36 wk of PCA. The percentage of time [mean (SD)] spent in QS at 32 wk of PCA was 33.5 (2.6) % for the NIDCAP group and 33.3 (6.9)% for the control infants (ns). At 36 wk, the corresponding values were 24.5 (3.2)% and 25.7 (4.7)%, respectively (ns). The number of QS periods/24 h decreased equally in both groups in association with maturation: from 24.6 (3.3) to 16.8 (1.8) and from 25.0 (5.8) to 17.5 (3.3), at 32 wk, and 36 wk of PCA, respectively (NS).

Conclusions: There were no indications of increased QS at 32 or 36 wk of postconceptional age among VLBW infants who received care based on NIDCAP.
Localized thigh swelling mimicking a neoplastic process: involvement of coxsackie virus type A21
Authors: Dekel B , Yoeli R , Shulman L , Padeh S , Passwell JH
Published: August 2010

A 4‐y‐old girl was admitted because of a left leg limp with an isolated swollen upper thigh and normal muscle enzymes. A radioisotope scan showed increased uptake especially in the bone and soft tissue of the left thigh, while magnetic resonance imaging of that region demonstrated widespread oedema in striated muscle. On muscle biopsy perivascular infiltrates were demonstrated but muscle fibres were not shown to be affected. Sequence analysis of reverse transcription‐polymerase chain reaction amplified fragments from the 5′‐non‐coding region of human enteroviruses identified a local strain of coxsackie virus A21 in the muscle. Clinical symptomatology subsided with oral steroids.

Conclusion: Local swelling mimicking a neoplasm may be related to infestation of coxsackie virus in muscle tissue.
Kostmann disease—infantile genetic agranulocytosis: historical views and new aspects
Authors: Zetterström Rolf
Published: August 2010

The results in the main reports on infantile genetic agranulocytosis or Kostmann Syndrome are summarized. New views on the pathogensis of the syndrome are given in a recent paper by Pütsep et al. Kostmann syndrome may cause early onset Group B streptococcal neonatal sepsis as reported in this issue of Acta Paediatrica (9).

Conclusion: Patients with Kostmann Syndrome who are successfully treated for agranulocytosis with serum colony stimulating factor remain deficient in cathelin‐LL‐37, a peptide antibiotic, which is normally present in neutrophils and saliva. This deficiency may explain that patients who are successfully treated for angranulocytosis continue to suffer from oral infections such as chronic periodontitis.
Weight reference charts for British long‐term breastfed infants
Authors: Cole TJ , Paul AA , Whitehead RG
Published: August 2010

Aim: To produce a modification of the British 1990 weight reference reflecting the growth of long‐term breastfed infants. Methods: 120 infants from the Cambridge Infant Growth Study fed breast milk (with no formula) for at least 24 wk, with solids introduced at a mean age of 15 wk, were weighed every 4 wk from birth to 52 wk. Weights were converted to standard deviation scores (SDS) for gender and age post‐term based on the revised British 1990 reference, averaged and smoothed across age, and then converted back to weights to provide modified median weight curves by gender. Other centile curves were constructed assuming the same variability and skewness by age as for the British reference. Results: Long‐term breastfed infants were slightly heavier than the reference at birth and crossed centiles upwards to reach +0.3 SDS at 2 mo, but subsequently crossed centiles downwards to −0.2 SDS by 12 mo.

Conclusion: The British 1990 reference, although better than previous growth standards, reflects the growth of long‐term breastfed infants only imperfectly, with mean weight falling by 0.5 SDS from 2 to 12 mo. The provision of breastfeeding‐specific centiles, either as a transparent overlay or as an alternative chart, should be useful for professionals and parents to monitor the weight of long‐term breastfed infants.
Lipoprotein(a) as a potent risk indicator for early cardiovascular disease
Authors: Dirisamer A , Widhalm K
Published: August 2010

Aim: Elevated levels of lipoprotein (a) [Lp(a)] are associated with increased cardiovascular risk in adults. It is not known whether Lp(a) elevation can be regarded as an additional risk factor even in children and adolescents. Therefore the purpose of this study was to compare the serum concentrations, distribution and frequency of Lp(a) and lipids of children and adolescents with premature parental and/or grandparental cardiovascular disease (CVD) with controls. Methods: 103 children and adolescents, aged 6–18 y, from families with premature CVD in a parent and/or grandparent, i.e. before the age of 55 y, and 103 controls were estimated for lipids and Lp(a). Results: Mean levels of total cholesterol (TC), low‐density lipoprotein cholesterol (LDL‐C) and Lp(a) were significantly higher in the risk than in the control group. Median Lp(a) levels were 20 (10–61.5) mg dl‐1 in the risk subjects, and 15 (6–26.5) mg dl‐1 in the control subjects (p= 0.005). Mean TC and LDL‐C concentrations of the risk group compared with the control group were 211 mg dl‐1 (5.5 mmol l‐1) versus 165 mg dl‐1 (4.3 mmol l‐1) (p > 0.0001), and 140 mg dl‐1 (3.6 mmol l‐1) versus 101 mg dl‐1 (2.6 mmol l‐1) (p > 0.0001), respectively.

Conclusion: It may be important to estimate plasma Lp(a) levels in progeny with a familial history of premature CVD, because it seems possible to identify those subjects who are at greater risk for later CVD either with or without elevated LDL‐C levels.
Randomized controlled trial of heparin for prevention of blockage of peripherally inserted central catheters in neonates
Authors: Kamala F , Boo NY , Cheah FC , Birinder K
Published: August 2010

Aim: To determine whether the addition of heparin to total parenteral nutrition (TPN) fluid would prevent blockage of peripherally inserted central catheters (PICCs) in neonates. Methods: This was a randomized, double‐blind, controlled study of 66 eligible neonates with PICCs inserted for the administration of TPN. Infants were randomized to receive TPN containing either 1 IU ml‐1 of heparin (n= 35) or no heparin (n= 31). Results: There was no significant difference in the incidence of blocked catheters between the two groups of infants (heparin: 14.3%; no‐heparin: 22.6%, p= 0.4). Although a higher percentage (62.9%) of infants in the heparin group received a complete course of TPN successfully via PICC than those in the no‐heparin group (48.4%), the difference was not statistically significant (p= 0.3). There were no significant differences in the incidence of catheter‐related sepsis, hypertriglyceridaemia, hyperbilirubinaemia, coagulopathy or intraventricular haemorrhage between the two groups.

Conclusion: Addition of heparin to TPN fluid was not associated with a significant reduction in the incidence of blocked PICCs. However, the sample size of this study was too small to exclude even rather marked differences between the groups.
Delayed disclosure and disrupted communication during forensic investigation of child sexual abuse: a study of 47 corroborated cases
Authors: Sjöberg RL , Lindblad F
Published: August 2010

Aim: To study factors of relevance for the understanding of disclosure of child sexual abuse. Methods: Cases from a Swedish district court involving 47 children in which allegations of child sexual abuse had been corroborated by a confession from the defendant were studied. Results: Delayed disclosure was related to a close relationship with the perpetrator and young age at the first experience of abuse. Disrupted communication during the police interview was related to less violent abuse.

Conclusion: The findings highlight the importance of social factors in children's disclosure of sexual abuse.
Neonatal cholestasis and infantile Gaucher disease: a case report
Authors: Barbier C , Devisme L , Dobbelaere D , Noizet O , Nelken B , Gottrand F
Published: August 2010

Aim: To report on clinical complications of liver disease occurring during Gaucher disease. Methods: A case of Gaucher disease was revealed by neonatal cholestasis and early onset of portal hypertension. Results: At 7 d of age, a newborn was admitted for cholestasis associated with hepatosplenomegaly and thrombocytopenia. At that time, bone marrow aspirate and liver biopsy did not reveal any engorged cells. The clinical course was marked by early progressive portal hypertension, and the patient died of uncontrollable upper gastrointestinal bleeding. The histological results of the postmortem showed that Gaucher cells were present in the liver, spleen and bone marrow. The diagnosis was confirmed by enzymatic studies.

Conclusion: Isolated neonatal cholestasis could be the first sign of Gaucher disease. Gaucher disease should always be considered in such circumstances, even if, initially, the bone marrow aspirate and liver biopsy do not reveal any engorged cells.
Effect of different types of feeding on fatty acid composition of erythrocyte membrane lipids in full‐term infants
Authors: Minda H , Molnár S , Bums I , Decsi T
Published: August 2010

Significantly higher levels of arachidonic acid (AA) and docosahexaenoic acid (DHA) in plasma lipids have previously been reported in 2 to 8‐wk‐old as well as in 6 to 12‐mo‐old full‐term infants fed exclusively human milk than in infants exclusively receiving formula without AA and DHA. However, in real life many infants receive both human milk and breast milk substitute formula. Healthy, full‐term infants aged 2 to 12 mo and fed exclusively human milk (n= 29, age: 29.2 [14.6] wk, mean [SD], no human milk substitute formula), exclusively formula without AA and DHA (n= 30, age: 26.6 [15.2] wk, no human milk after the age of 1 mo) or combined diet (n= 38, age: 30.3 [12.8] wk, human milk for >1 mo and breast milk substitute formula) were investigated in this cross‐sectional study. Fatty acid composition of erythrocyte membrane phosphatidylethano‐lamine (PE), phosphatidylcholine and sphingomyeline lipids was determined by high‐resolution capillary gas‐liquid chromatography. The most pronounced diet‐related differences were seen in PE lipids. Values of PE α‐linolenic acid (0.07 [0.05] vs 0.26 [0.18] vs 0.19 [0.19], median [range from the 1st to the 3rd quartile], exclusively breastfed vs. exclusively formula fed vs combined diet), eicosapentaenoic acid (0.19 [0.13] vs 0.35 [0.23] vs 0.27 [0.31]) and dihomo‐γ‐linolenic acid (1.34 [0.42] vs 1.86 [0.62] vs 1.58 [0.73]) were significantly lower in exclusively breastfed infants than in those fed formula, exclusively or partially. In contrast, PE AA (26.48 [2.50] vs 24.34 [4.74] vs 24.94 [3.64]) and DHA (4.93 [2.91] vs 3.51 [2.14] vs 3.58 [2.27]) values were significantly higher in exclusively breastfed infants than in the other two groups.

Conclusion: In full‐term infants aged 2 to 12 mo, erythrocyte membrane AA and DHA values are significantly higher with exclusive breastfeeding than with partial breastfeeding or exclusive feeding of formula without AA and DHA.
New approach to osteopenia in phenylketonuric patients
Authors: Pérez‐Dueñas B , Cambra FJ , Vilaseca MA , Lambruschini N , Campistol J , Camacho JA
Published: August 2010

Aim: To study bone mineralization in a group of phenylketonuric patients and to search for a possible relationship between bone mineral density, dietary control, serum minerals and nutrition intake. The response to treatment with low‐dose 1.25‐(OH)2 vitamin D in patients with osteopenia was evaluated. Methods: Twenty‐eight phenylketonuric patients (age range: 10–33 y) on dietary treatment were investigated. Bone density at the lumbar spine (Dual Energy X‐ray Absorptiometry), bone formation markers (osteocalcin and bone alkaline phosphatase), serum minerals, index of dietary control and protein, vitamin D and mineral intakes were determined. Results: Of the patients studied, 78.6% had good dietary compliance (462 ± 89 μmol/L). Mean protein, vitamin D and mineral intakes met the recommended dietary allowances (RDAs). Nevertheless, 8 patients had calcium intakes lower than 1000 g/d, and a positive correlation between Z‐score and calcium (r= 0.585; p= 0.002) or phosphorus intake (r= 0.546; p= 0.005) was observed. Osteopenia was detected in 14 patients (50%). Moreover, bone alkaline phosphatase in phenylketonuric patients older than 18 y of age was significantly lower than that in controls (p > 0.0001). No correlation was found between bone mineral density, age, serum minerals, bone formation markers or index of dietary control. Treatment with 0.25 μg/d calcitriol significantly increased bone density in 6 patients.

Conclusion: A defect in bone mineralization was detected in 50% of patients in our series. The correct amount of formula intake seems to be necessary for bone mineralization in phenylketonuric patients. Calcitriol can be a useful treatment for these patients, although more studies are needed to confirm these results. Hypercalcaemia and hypercalciuria need to be carefully monitored.
Inhibitors in the Swedish population with severe haemophilia A and B: a 20‐year survey
Authors: Knobe KE , Sjörin E , Tengborn LI , Petrini P , Ljung RCR
Published: August 2010

Aim: To survey the entire population (n= 116) afflicted with severe haemophilia A or B born in Sweden over a 20‐y period (1980–1999), and to examine the epidemiological, genetic and clinical aspects of development of inhibitors to factors VIII and IX (FVIII/FIX). Methods: One hundred of the subjects had haemophilia A and 16 had haemophilia B. All of these subjects had received prophylactic treatment and had a check‐up of inhibitor status at least twice a year. Sixty‐one were born between 1980 and 1989 and 55 between 1990 and 1999. Results: Nineteen percent (19/100) of those with haemophilia A and 37% (6/16) with haemophilia B developed inhibitors at 12–18 mo of age, after exposure to FVIII/FIX concentrates for an average of 14 d in the case of haemophilia A and 16 d in haemophilia B. All patients with inhibitors carried mutations that impaired protein synthesis. The high incidence of FIX inhibitors may have been due to the large number of complete deletions (13%) in the Swedish haemophilia B population. Patients with haemophilia A showed no significant increase (p= 0.65) in incidence of inhibitors (n= 10/48, total incidence 21%) in the 1990s, when they were treated mainly with recombinant products, as compared to the 1980s (n= 9/52,17%), when they received intermediate/high‐purity plasma‐derived concentrates.

Conclusion: Our population‐based study verifies that genotype has a general impact on the incidence of FVIII/FIX inhibitors, and that recombinant FIII/FIX concentrates are not a predisposing factor for inhibitor development.
Neutrophil regeneration precedes healing of tissue destruction, as indicated by serum C‐reactive protein, in children with cancer recovering from neutropenic fever
Authors: Vettenranta K , Hovi L , Mäkipernaa A , Jalanko H , Saarinen‐Pihkala UM
Published: August 2010

Aim: To evaluate the relationship between absolute neutrophil count and C‐reactive protein (CRP) in the recovery phase of neutropenic fever among paediatric patients with cancer. Methods: A total of 102 paediatric oncology patients with 177 episodes of fever and neutropenia was studied prospectively in a two‐centre setting. Antimicrobial therapy was discontinued 9 d (mean) post‐initiation with a mean absolute neutrophil count of 1.8 ± 109l‐1 and CRP of 32 mg l‐1. Results: The mean level of CRP below 20 mg l‐1 was reached on day 12. The level of CRP peaked on the day following the commencement of antimicrobial therapy. Throughout the episodes of fever and neutropenia higher levels of CRP were associated with a lower absolute neutrophil count. Following defervescence the pace of marrow recovery as evidenced by an increasing absolute neutrophil count to < 0.2 and < 0.5 ± 109l‐1 was more rapid than the normalization of serum CRP. There was a 2–3 d lag period between absolute neutrophil count exceeding the level of 200 ± 106l‐1 and the return of CRP to a baseline level. All episodes were treated successfully and there were no fatalities.

Conclusion: Among patients recovering from neutropenia and fever the signs of marrow recovery remain the key criterion in evaluating the safety of discontinuing antimicrobial therapy, with serum CRP remaining more of an indicator of ongoing tissue repair.
Effect of Dry Bed Training on behavioural problems in enuretic children
Authors: HiraSing RA , van Leerdam FJM , Bolk‐Bennink LF , Koot HM
Published: August 2010

Children with nocturnal enuresis (n= 91) selected by school doctors in the Netherlands from 1991 to 1994 were included in a study to assess the course of behavioural problems especially when the children became dry after the Dry Bed Training (DBT) programme. The Child Behaviour Checklist (CBCL) questionnaire was completed by 88 parents (96%) prior to DBT (T1) and by 83 parents (91%) 6 mo after DBT (T2). The mean CBCL total problem score at T1: 24.0 (range 2–91, SD 16) was significantly higher than that of a Dutch norm group: 20.45, (p= 0.025). Compared to T1, the mean CBCL total problem score at T2 was 16.8 (range 0–73; SD 14.7; p > 0.0001). Of the children with CBCL total problem scores at T1 in the borderline or clinical range, 92% became dry and 58% improved to the normal range. At T2, the children seemed to have less internal distress, fewer problems with other people, and were less anxious and/or depressed.

Conclusion: Children with behavioural/emotional problems who wet their beds need not first be treated for their behavioural/emotional problems. Bedwetting can be treated successfully with DBT when other treatments such as normal alarm treatment have failed, and alarm treatment/DBT can have a positive influence on behavioural/emotional problems.
Findings in familial haemophagocytic lymphohistiocytosis prior to symptomatic presentation
Authors: Hafsteinsdóttir S , Jónmundsson GK , Kristinsson JR , Winiarski J , Henter J‐I , Haraldsson Á
Published: August 2010

Familial haemophagocytic lymphohistiocytosis (FHL) is a rare, autosomal recessive disease of infancy and early childhood clinically characterized by fever, hepatosplenomegaly, lymphadenopathy, rash, neurological symptoms and icterus. Common laboratory findings include cytopenia, elevated liver enzymes, hyperbiliriubinaemia, hypofibrinogenaemia and hypertriglyceridaemia. The natural killer cell function is frequently decreased or absent. A diffuse lymphohistiocytic infiltration is seen in the reticuloendothelial system, often with haemophagocytosis. Molecular diagnosis is available in a minority of FHL families. Without adequate treatment and bone‐marrow transplantation, the disease is fatal. A 6‐wk‐old child with FHL is presented. Shortly before the clinical onset of the disease, blood testing and bone‐marrow examination had been carried out. All results were considered normal at that time.

Conclusion: Blood tests and bone‐marrow examination may be normal shortly before the clinical presentation and therefore do not exclude the diagnosis of FHL. There is a need for extended molecular diagnostic possibilities.
Plasma homocysteine and lipoprotein (a) levels as risk factors for atherosclerotic vascular disease in epileptic children taking anticonvulsants
Authors: Türner L , Serdaroǧlu A , Hasanoǧlu A , Biberoǧlu G , Aksoy E
Published: August 2010

Aim: To assess the effect of anticonvulsant treatment on plasma homocysteine level and lipoprotein (a) in epileptic children. Methods: Plasma total homocysteine, folate, vitamin B12 and lipoprotein (a) concentrations were measured in 111 epileptic children taking anticonvulsant drugs for longer than 12 mo. Forty‐six healthy, sex‐ and age‐matched children served as controls. Results: Patients and controls differed significantly in concentrations of homocysteine (p > 0.05) and lipoprotein (a) (p > 0.001). The number of patients with homocysteine concentrations of >9 μM was significantly higher in the patient group than in the control group. A significant inverse relationship was found between vitamin B12 folate levels and plasma homocysteine levels in the patient group; 28.8% of the patient group had lipoprotein (a) concentrations above the cutoff value (30mg/dl) for increased risk of early atherosclerosis, whereas none of the control patients had concentrations above this value.

Conclusion: These data indicate that prolonged anticonvulsant treatment could increase plasma homocysteine and lipoprotein (a) concentrations and that it may be useful to measure the levels routinely in order to prevent atherosclerosis in epileptic children taking anticonvulsant drugs.
Dietary supplementation of long‐chain polyunsaturated fatty acids in preterm infants: effects on cerebral maturation
Authors: van Wezel‐Meijler G , van der Knaap MS , Huisman J , Jonkman EJ , Valk J , Lafeber HN
Published: August 2010

Aim: To study the influence of dietary‐supplied long‐chain polyunsaturated fatty acids on structural brain maturation in preterm infants and to investigate parameters of functional brain development, relating them to structural maturation. Other studies have suggested that dietary supplementation of long‐chain polyunsaturated fatty acids in preterm infants may enhance their visual development. The influence on structural brain development has never been evaluated. Methods: In a prospective, double‐blind study, 42 formula‐fed premature infants were randomized to be fed either a standard preterm formula without long‐chain polyunsaturated fatty acids or an identical formula supplemented with docosahexaenoic acid (0.015 g/100 ml) and arachidonic acid (0.031 g/100ml). Infants with significant cerebral damage, retinopathy, chronic disease or feeding problems were excluded. Follow‐up was focused on assessment of cerebral myelination by MRI. Psychomotor, mental and visual development was analysed and flash‐visual evoked potentials were recorded. Results: It was found that progress of myelination, mental and motor development and latencies of visual evoked potentials were not positively influenced by supplementation of long‐chain polyunsaturated fatty acids. At each test age, visual acuity was slightly better in the supplemented infants than in the non‐supplemented infants, but the difference never reached significance level

Conclusion: Supplementation of long‐chain polyunsaturated fatty acids did not have a demonstrable positive influence on structural brain maturation. Related to this finding, in this small cohort of preterm infants without significant neurological damage, sample size being restricted by strict inclusion criteria and MRI procedures, no significant positive effects were found on psychomotor, mental and visual development.
Predictors of coping strategy selection in paediatric patients
Authors: Landolt MA , Vollrath M , Ribi K
Published: August 2010

Aim: To assess the prevalence of specific coping strategies and predictors of coping strategy selection in 179 patients (mean age= 10.2 y). The children were investigated one month after the occurrence of an accident (n= 105), diagnosis of cancer (n= 26) or diagnosis of diabetes mellitus type I (n= 48). Results: Patients used a great variety of coping strategies. The most frequent strategies were cognitive avoidance, positive cognitive restructuring and avoidant actions. The strategies of seeking problem‐focused support and emotion‐focused support were rarely used. Diagnostic category, length of hospital stay, and gender were not associated with coping strategy use. Age, socioeconomic status and functional status of the patient were found to predict coping strategy selection. Younger children made less use of active coping, distraction and seeking support. Patients of lower socioeconomic status used religious coping strategies significantly more often, whereas patients with lower functional status used avoidance and support‐seeking strategies more often.

Conclusion: In this study it was found that paediatric patients used a wide variety of coping strategies, irrespective of diagnosis and gender. Age of the child and functional status were the most important predictors of coping strategy selection.
Treatment of children with cystic fibrosis: central, local or both?
Authors: van Koolwijk LME , Uiterwaal CSPM , van der Laag J , Hoekstra JH , Gulmans VAM , van der Ent CK
Published: August 2010

Owing to a lack of longitudinal studies, the effect of centralization of care on pulmonary function and survival remains unclear. Three different levels of involvement of centralized care in the treatment of paediatric cystic fibrosis patients were compared with regard to longitudinal pulmonary function and nutritional and microbiological status in a 3‐y period, and the literature was reviewed on the possible advantages and disadvantages of centralized care. The study included 105 paediatric patients attending the Cystic Fibrosis Centre between January 1997 and January 2001. Twenty‐three patients were treated by local paediatricians according to the protocol of the Centre and were seen only once a year at the Centre, for an annual check‐up (local care). Forty‐one patients were treated at the Centre only (centralized care). The remaining 41 patients were treated in close cooperation between the Centre and local hospitals, with patients visiting the doctors alternately (shared care). The mean annual changes in pulmonary function and body mass index from all patients, as well as a microbiological survey, were reviewed. No significant differences were found between the three groups for annual changes in FEV1, FVC and body mass index, nor did the review of microbial colonization show any significant differences between the groups. Because the groups in this study were relatively small, the results might have been influenced by lack of power.

Conclusion: In this relatively small group, no differences in pulmonary function, nutritional status or microbiological colonization between the three levels of involvement of centralized care could be found. This could signify that local paediatricians have a special role in the care for patients with cystic fibrosis, in close cooperation with the specialists at the Centre.
Urge incontinence and voiding postponement in children: somatic and psychosocial factors
Authors: Lettgen B , von Gontard A , Olbing H , Heiken‐Löwenau C , Gaebel E , Schmitz I
Published: August 2010

Aim: To analyse the number of urinary tract infections, uroflowmetry, behavioural symptoms and intrafamilial interaction in two groups of daytime wetting children in a paediatric and a child psychiatric unit. Methods: Ninety‐four children with either voiding postponement (52) or urge incontinence (42) were examined prospectively for history of urinary tract infections (UTIs), uroflowmetry, the syndrome scales of the Child Behaviour Checklist (CBCL 4/18‐Achenbach) and the Family Adaptability and Cohesion Evaluation Scales (FACES‐III) (Olson) questionnaire. Results: Children with urge incontinence had a significantly higher rate of previous urinary tract infections (50%) than children with voiding postponement (19.2%; p > 0.001), who showed a high rate of plateau (12.2%) and staccato (20.4%) curves and were characterized by a wide variety of behavioural symptoms, including withdrawn (11.6%), aggressive (11.8%), delinquent (19.6%) behaviour and attention problems (13.7%). Clinically relevant behavioural scores were 4–10 times higher for the voiding postponers, and 2–3 times higher for children with urge incontinence. Furthermore, families of voiding postponers had significantly fewer balanced types of intrafamilial function (FACES‐III). Problematic “rigid/disengaged” and “rigid/separated” types predominated.

Conclusion: Urge incontinence is characterized by a higher rate of UTIs, a lower urine volume in uroflowmetry, a lower rate of behavioural scores in the clinical range and well‐functioning families. Voiding postponement children, on the other hand, have a higher, though not significant, rate of abnormal uroflow curves, a wide variety of clinically relevant behavioural symptoms, which were significantly higher for attention and delinquent problems. Conduct problems predominated; only 13.7% of the children had attention problems in the clinical range. The findings lend empirical support to the entity of voiding postponement as an acquired or behavioural syndrome characterized by wetting in association with a delay of micturition and other externalizing conduct problems.
Born small for gestational age: relation to future allergy and asthma
Authors: Hesselmar B , Dahlgren J , Wennergren G , Åberg N , Albertsson‐Wikland K
Published: August 2010

Aim: To evaluate whether intrauterine growth retardation (IUGR) protects against the development of allergy. Methods: A case‐control study of 1515 subjects (15–25 y), of whom 430 were cases (birthweight/length below – 2 SD for gestational age). Birth data were from the national birth register. The frequencies of allergic diseases were evaluated by questionnaire. Results: For the 950 who replied, the frequencies of allergic diseases were similar in cases and controls.

Conclusion: IUGR does not protect against the development of allergy.
Developmental biology of the dendritic cell system
Authors: Schibler KR , Georgelas A , Rigaa A
Published: August 2010

Aim: To determine whether an imbalance of dendritic cell subsets might contribute to diminished adaptive host responses observed in newborn infants. It was hypothesized that the proportion of lymphoid dendritic cells would be greater than that of myeloid dendritic cells in cord blood. Methods: To investigate this, dendritic cell subsets were evaluated in whole cord blood by flow cytometry. Circulating dendritic cells were also isolated from cord blood based on CD1c and BDCA‐2 expression. Myeloid dendritic cells were also obtained by culturing cord and adult blood monocytes. Surface phenotypes of these cells were determined by flow cytometry using monoclonal antibodies directed against lineage, major histocompatibility, adhesion, co‐stimulation and cytokine receptor molecules. Antigen‐presenting functions of dendritic cell subsets were determined by mixed leukocyte reactions. Results: Circulating myeloid dendritic cells were higher in cord blood than previously reported in adult blood, whereas lymphoid dendritic cell numbers were similar between cord and adult blood. Expression of CD11c, CD45RA and CD45RO did not accurately differentiate between dendritic cell subsets circulating in cord blood. Fresh and culture‐derived cord blood myeloid dendritic cells stimulated adult allogeneic leukocyte proliferation, while lymphoid dendritic cells were less effective inducers of an adult allogeneic leukocyte response. Culture‐derived dendritic cells induced modest autologous cord blood leukocyte proliferation, but freshly isolated myeloid and lymphoid dendritic cells did not stimulated autologous leukocytes.

Conclusion: Contrary to the hypothesis, an imbalance in the ratio of circulating myeloid to lymphoid dendritic cell subsets does not exist and, therefore, does not contribute to diminished adaptive immune responses in newborn infants.
Roles of erythropoietin in human milk
Authors: Kling PJ
Published: August 2010

Erythropoietin (Epo) is one of many biologically active growth factors present in human and animal milk. Accumulating evidence shows important developmental roles for these milk‐borne growth factors. Although Epo is present in biologically relevant amounts in mammalian milk, the roles of Epo in milk are incompletely defined. A significant proportion of milk‐borne Epo resists proteolytic degradation. Epo receptors (EpoR) have been found on gastric mucosa and intestinal mucosa, and in mesenteric vessel endothelium. Evidence to date shows that intact Epo reaches these local organs, as well as distal organs. After feeding Epo, local gastrointestinal physiological effects are seen in suckling rats. In humans and rats, short‐term feeding of high‐dose Epo increases reticulocytes, but it is unclear whether sustained treatment increases red cell mass.

Conclusion: Further work towards understanding the physiological and potential pharmacological roles of enterally administered Epo is necessary.

Evidence to date supports the theory that Epo is present in biologically relevant amounts in mammalian milk, is protected from gastrointestinal proteolytic degradation and probably plays a role in local neonatal gastrointestinal development. Animal data show that milk from hypoxic mothers appears to stimulate erythropoiesis better than pharmacological doses of Epo added to normal milk or formula. The lack of efficacy of pharmacological doses of rhEpo in studies to date may be secondary to several factors, including local utilization of the hormone, the need for Epo to work in conjunction with another hematopoietic growth factor in milk, or nutritional factors, such as iron deficiency, interfering with the rhEpo response. Whether milk‐borne Epo plays a significant role in stimulating erythropoiesis is still unclear and more work is necessary to determine the physiological and pharmacological roles of milk‐borne Epo.
Mechanisms underlying thrombocytopenia in the neonatal intensive care unit
Authors: Sola MC , Rimsza LM
Published: August 2010

Thrombocytopenia is one of the most common hematological problems among neonates in the neonatal intensive care unit (NICU), but in the majority of cases the kinetic mechanism responsible is unclear. This review focuses on both traditional and innovative methods used to evaluate the mechanisms responsible for thrombocytopenia in neonates, and analyzes the data generated from those methods.

Conclusion: Results of studies using new methods for evaluating thrombocytopenia, coupled with recent descriptions of marrow megakaryocyte mass, suggest that decreased platelet production complicates most cases of thrombocytopenia among neonates in the NICU.
Use of the bleeding time in the neonatal intensive care unit
Authors: Vecchio A Del
Published: August 2010

Impairments of primary hemostasis are frequently responsible for serious bleeding in sick infants in the neonatal intensive care unit (NICU). Therefore, a rational approach to these infants with hemorrhagic manifestations, in addition to an accurate medical history, a careful physical examination and routine screening coagulation tests, may include a bleeding time. The bleeding time is the traditional in vivo test for assessing primary hemostasis. It is a useful clinical tool to detect quantitative or qualitative platelet disorders or microvascular defectiveness. Its diagnostic value in neonates is controversial, mainly owing to limited experience in executing the test, which is performed uncommonly in the NICU. Using a template device expressly adapted for neonates (Surgicutt Newborn), a small incision 2.5 mm long and 0.5 mm deep provides a standardized, reproducible and sensitive bleeding time, with minimal scarring and pain. Various hereditary or acquired maternal and neonatal diseases, as well as some antepartum medications given to the mother or drugs commonly used to treat NICU patients, such as indomethacin, ibuprofen, penicillin compounds and theophylline, can impair primary hemostasis and consequently prolong the bleeding time in neonates. Furthermore, other factors distinctive to neonates, including gestational age, the increased von Willebrand factor concentration and function, high hematocrit, the large size of erythrocytes and platelet hyporeactivity in the first 10 d of life, affect plateletvessel wall interaction and influence the interpretation of bleeding time results in newborn infants. Because the clinical evaluation of primary hemostasis consists of complex laboratory testing, largely reserved for specialized laboratories and currently not routinely performed in newborn infants, automated bleeding time devices specifically generated to make standardized and acceptably small incisions in newborn infants have become a surrogate.

Conclusion: With awareness of its value and limitations, the bleeding time can be included in the baseline evaluation of neonates in the NICU, for guiding diagnosis and treatment of primary hemostatic disorders.
What is the rationale for the use of granulocyte and granulocyte‐macrophage colony‐stimulating factors in the neonatal intensive care unit
Authors: La Gamma EF , De Castro MH
Published: August 2010

Neonatal sepsis remains an unsolved major contributor to morbidity and mortality. In the 1980s the promise of augmenting immune function using pooled intravenous gammaglobulin to supplement the exceedingly low levels of immunoglobulin G in premature infants failed to demonstrate a clear advantage. Similarly, cytokine augmentation of cellular function in the 1990s largely appeared to be suffering the same fate. However, both results may arise from a problem in experimental design where the combination of both treatments may be necessary along with specific antibody. For example, in vitro, independently of an array of other humoral and cellular immature immune system issues, opsonization of bacteria is improved in the presence of antibody. The question is whether the same result can be achieved in vivo. No experiments have been reported that directly test this hypothesis.

Conclusion: More investigation is needed in this challenging area of neonatal research.
Perinatal aspects of iron metabolism
Authors: Rao R , Georgieff MK
Published: August 2010

Iron sufficiency is critical for rapidly developing fetal and neonatal organ systems. The majority of iron in the third trimester fetus and the neonate is found in the red cell mass (as hemoglobin), with lesser amounts in the tissues as storage iron (e.g. ferritin) or functional iron (e.g. myoglobin, cytochromes). Iron is prioritized to hemoglobin synthesis in red cells when iron supply does not meet iron demand. Thus, non‐heme tissues such as the skeletal muscle, heart and brain will become iron deficient before signs of iron‐deficiency anemia. Gestational conditions that result in lower newborn iron stores include severe maternal iron deficiency, maternal hypertension with intrauterine growth retardation and maternal diabetes mellitus. Stable, very low birthweight premature infants are also at risk for early postnatal iron deficiency because they accrete less iron during gestation, grow more rapidly postnatally, are typically undertreated with enteral iron and receive fewer red cell transfusions. Conversely, iron overload remains a significant concern in multiply transfused sick preterm infants because they have low levels of iron‐binding proteins and immature antioxidant systems.

Conclusion: The highly variable iron status of preterm infants combined with their risk for iron deficiency and toxicity warrants careful monitoring and support in the newborn and postdischarge periods.

Iron metabolism undergoes major changes during the last trimester and early postnatal period, at a time when the infant is particularly sensitive to both iron deficiency and iron overload. Various prenatal conditions affect the iron load at birth, including maternal iron deficiency, maternal hypertension with fetal growth restriction, maternal diabetes mellitus and preterm delivery. Since iron is prioritized to red cells in the fetus and neonate, other organs such as the liver, heart and brain can potentially suffer from iron deficiency when iron supply does not meet iron demand. In the postnatal period, the premature infant is placed at earlier risk of iron deficiency because of rapid growth rates, uncompensated iron losses from phlebotomy and low nascent iron stores. Conversely, the immature antioxidant systems and low total iron‐binding capacity of the preterm infant increase the risk of potential toxicity from iron.
New biomarkers of fetal‐neonatal hypoxic stress
Authors: Perrone S , Bracci R , Buonocore G
Published: August 2010

The complex pathophysiological mechanisms underlying perinatal hypoxia make it difficult to define early markers of severe hypoxia‐ischemia encephalopathy. However, as progress in the development of neuroprotective therapeutic measures continues, the early identification of neonates at risk of severe hypoxic‐ischemic encephalopathy is an important goal for appropriate decision making. Although the timing of perinatal hypoxic brain damage may vary and is sometimes unknown, high levels of non‐protein‐bound iron and high nucleated red blood cell counts in cord blood indicate an antepartum origin of neurological impairment, because they can occur only as a consequence of a pre‐existing asphyxic event.

Conclusion: The combined assessment of nucleated red blood cells and non‐protein‐bound iron at birth seems extremely useful for the early identification of newborns at high risk of brain damage. Activin A also seems to be a reliable marker of perinatal hypoxia. Prospective long‐term follow‐up studies are needed to verify their predictive role.
Electrocardiographic signs of hypertrophy in Fabry disease‐associated hypertrophic cardiomyopathy
Authors: Kampmann C , Wiethoff CM , Martin C , Wenzel A , Kampmann R , Whybra C , Miebach E , Beck M
Published: August 2010

Aims: Fabry disease results from deficient activity of the lysosomal enzyme α‐galactosidase A. Progressive accumulation of the major substrates leads, in both men and women, to progressive hypertrophic cardiomyopathy. We aimed to evaluate the utility of different electrocardiographic (ECG) parameters for assessing the degree and severity of hypertrophic cardiomyopathy in patients with Fabry disease. Methods: A total of 166 ECGs of 94 hemi‐ and heterozygous patients with Fabry disease were analysed and compared with echocardiographic‐estimated left ventricular mass (LVM). Results: There was a significant (p > 0.0001) correlation between QRS duration (R2= 0.59), 12‐lead amplitude/duration product (R2= 0.61), Sokolow‐Lyon voltage/duration product (R2= 0.52) and LVM. Analysis of receiver operating characteristics revealed that the 12‐lead amplitude/duration product had the highest sensitivity‐specificity relationship (p > 0.01 compared with the Cornell index).

Conclusion: In general, ECG signs of left ventricular hypertrophy correlated well with LVM as revealed by echocardiography. Of the parameters studied, the 12‐lead amplitude/duration product was the most successful at describing the severity of cardiac involvement in Fabry disease. These data suggest that ECG parameters have potential for use as a simple and cost‐effective means of screening for hypertrophic cardiomyopathy in patients with Fabry disease.
Isolated cardiac manifestations in Fabry disease: the UK experience
Authors: Sachdev B , Elliott PM
Published: August 2010

Cardiac abnormalities are common in patients with Fabry disease, and may be the only clinical manifestation of the disease in some patients. At St George's Hospital Medical School, a national referral centre for hypertrophic cardiomyopathy in the UK, a study of 153 consecutively referred male patients revealed that 4% had Fabry disease. This increased to 6% in patients over 40 years of age. All these patients had electrocardiographic (ECG) abnormalities, most of which were consistent with those found in patients with classic Fabry disease: left ventricular hypertrophy, repolarization abnormalities and a prolonged QRS complex. A study of heterozygote females with Fabry disease also showed ECG and echocardiographic abnormalities in most patients.

Conclusions: Fabry disease should be considered in the differential diagnosis of otherwise unexplained cardiac disease.
Mechanisms of neuropathic pain and their importance in Fabry disease
Authors: Birklein F
Published: August 2010

One of the most prominent features of Fabry disease is neuropathic pain. Neuropathic pain occurs after neuronal damage. In contrast to inflammatory or trauma‐related pain, which normally helps to maintain or restore body functions, neuropathic pain tends to become chronic, and must therefore be considered a ‘pathological’ pain. Neuropathic pain has usually been classified according to the aetiology of nerve damage: traumatic, inflammatory, cancer‐related or metabolic (e.g. Fabry disease). However, use of this classification often results in inadequate therapy for neuropathic pain. Recent research has revealed distinct mechanisms that are responsible for neuropathic pain. These mechanisms are independent of the aetiology of nerve damage. The most important mechanisms are accumulation and maldistribution of sodium channels on injured axons, pathological sympathoafferent coupling, disinhibition of nociception and central or peripheral nociceptive sensitization.

Conclusions: Future research should focus on diagnostic tools to identify the predominant mechanisms in individual patients. These mechanism could be targeted specifically by drugs, or non‐drug therapy, enabling more effective treatment of neuropathic pain.
Evaluation of peripheral and autonomic nerve function in Fabry disease
Authors: Hilz MJ
Published: August 2010

The neurological manifestations of Fabry disease include severe episodes of lancinating pain and burning paraesthesias in the extremities, often triggered by changes in temperature. The preferential involvement of small nerve fibres and the accumulation of storage product in the central autonomic nervous system and autonomic ganglia means that standard neurophysiological procedures cannot adequately evaluate the peripheral and autonomic nervous systems of affected patients. This paper describes the various methods that have been developed to assess impairment of temperature perception, vibratory perception, sudomotor and sweat gland function, and limb and superficial skin blood flow and vasoreactivity. These methods, including thermal provocation tests, quantitative sudomotor axon reflex testing and venous occlussion plethsmography, have been used effectively in patients with Fabry disease to measure the extent of neurological dysfunction.

Conclusions: Effective methods for measuring neurological involvement in patients with Fabry disease have been developed. These methods will be valuable in assessing the response of patients to enzyme replacement therapy.