Practice variation among Dutch paediatricians in palivizumab prescription rates: the importance of parental counselling approach.

AIM: To investigate differences in palivizumab prescription rates between Dutch paediatricians, and the role of parent counselling in this practice variation. METHODS: A retrospective chart review of premature infants <32 weeks of gestation, aged less than six months at the start of the winter season, born between January 2012 and July 2014, in three secondary hospital-based paediatric practices in the Netherlands. RESULTS: We included 208 patients, 133 (64%) of whom received palivizumab. Prescription rates varied considerably between the three hospitals: 8% (6/64), 89% (32/36) and 99% (97/98). A noticeable difference in the way parents were counselled about palivizumab was the use of the number needed to treat (NNT). In the hospital with the lowest prescription rate (8%), an NNT of 20 to prevent one hospitalisation was explicitly discussed with parents. Bronchiolitis-related hospital admissions occurred in 11.3% of patients receiving palivizumab compared to 20.0% in nonimmunised infants (p = 0.086). CONCLUSION: Considerable practice variation exists among Dutch paediatricians regarding palivizumab prescription rates. The counselling method seems to play an important role. Presenting palivizumab prophylaxis as a preference-sensitive decision, combined with the explicit use and explanation of an NNT, leads many parents to refrain from respiratory syncytial virus immunisation.

Hypnotherapy or transcendental meditation versus progressive muscle relaxation exercises in the treatment of children with primary headaches: a multi-centre, pragmatic, randomised clinical study.

Many children suffer from headaches. Since stress may trigger headaches, effective techniques to cope with stress are needed. We investigated the effectiveness of two mind-body techniques, transcendental meditation (TM) or hypnotherapy (HT), and compared them with progressive muscle relaxation (PMR) exercises (active control group). Children (9-18 years) suffering from primary headaches more than two times per month received either TM (N = 42), HT (N = 45) or PMR (N = 44) for 3 months. Primary outcomes were frequency of headaches and ≥ 50% reduction in headaches at 3 and 9 months. Secondary outcomes were adequate relief, pain coping, anxiety and depressive symptoms, somatisation and safety of treatment. Groups were comparable at baseline. Headache frequency was significantly reduced in all groups from 18.9 days per month to 12.5 and 10.5 at respectively 3 and 9 months (p < 0.001), with no significant differences between the groups. Clinically relevant headache reduction (≥ 50%) was observed in 41% and 47% of children at 3 and 9 months respectively, with no significant differences between the groups. No differences were observed in secondary outcome measures between the intervention groups. No adverse events were reported.Conclusion: All three techniques reduced primary headache in children and appeared to be safe.Trial registration: NTR 2955, 28 June 2011 ( www.trialregister.nl ) What is Known: • Stress may be an important trigger for both tension type headache and migraine in children. • Good data are lacking on the effect of transcendental meditation, hypnotherapy or progressive muscle relaxation as possible stress-reducing therapies in children with primary headaches. What is New: • Three non-pharmacological techniques, i.e., transcendental meditation, hypnotherapy and progressive muscle relaxation exercises, all result in a clinically significant reduction of headaches and use of pain medication. • No large differences between the three techniques were found, suggesting that children can choose either one of the three techniques based on personal preferences.

[A neonate with the 'blueberry muffin syndrome']. / Een neonaat met het 'blueberry muffin' syndroom.

A term born girl showed livid papules and macules disseminated over her body, directly postpartum. She was examined by the pediatrician, who recognized this as the 'blueberry muffin syndrome'. Blood examination showed a modest increase of erythroblasts. Skin biopsy indicated the presence of hematologic malignancy. Bone marrow puncture revealed the diagnosis 'acute myeloid leukemia'. Other causes of the blueberry muffin syndrome are congenital infections, neuroblastoma and rhabdomyosarcoma.

[Pustular and vesicular skin eruptions in newborns]. / Puistjes en blaasjes bij pasgeborenen.

Four neonates with vesicopustular skin eruptions, 1 girl and 3 boys, were diagnosed with feeding blisters, bullous impetigo, erythema toxicum neonatorum and transient neonatal pustular melanosis, respectively. The neonate with bullous impetigo was treated with antibiotics; the remaining neonates were not treated. The neonate with transient neonatal pustular melanosis developed hyperpigmentation, whereas the other neonates recovered without sequelae. Skin lesions in neonates are common and frequently cause parental concern. Most causes of neonatal pustular and vesicular skin eruptions are benign and transient. However, some skin lesions must be recognised and treated rapidly. Therefore it is important to identify these neonatal skin eruptions based on a thorough history of the mother and child and clinical presentation. Skin culture may be helpful in some cases.

[Developmental delay in breastfed children due to inadequate diet of the mother]. / Ontwikkelingsachterstand bij borstgevoede kinderen door ontoereikend dieet van de moeder.

Two infant boys of 7 and 12 months respectively who presented with symptoms of failure to thrive and developmental delay were diagnosed with vitamin B12 deficiency. This deficiency is a rare condition in infants living in developed countries. It does occur, however, in infants who are breastfed by mothers with an inadequate diet. Both of the children studied were breastfed by vegetarian mothers. Following vitamin suppletion, both children showed signs of recovery. The importance of considering vitamin deficiencies in similar infants presenting with failure to thrive is emphasized. Moreover, maternal dietary habits in breastfed children should be checked. To prevent irreversible neurological damage, early recognition of any nutritional deficiencies is important.

Behavioural factors related to metabolic control in patients with phenylketonuria.

BACKGROUND: The objective of this study was to determine the importance of parental factors possibly related to dietary control in early and continuously treated patients with phenylketonuria (PKU). METHODS: A questionnaire was disseminated among parents of 238 patients with PKU born after the nationwide introduction of newborn screening for PKU (1 September 1974) until 31 December 1995. The questionnaire was based on a behavioural model measuring people's attitudes, subjective norms, and self-efficacy. Dietary control was defined on the basis of mean phenylalanine (Phe) concentration of the PKU patients measured between 1 January 1994 and 31 December 1996. RESULTS: Response rate was 71%. Attitudes: children of parents who believed that their child adheres well to the diet, even if his or her Phe concentrations are sometimes too high, had lower Phe concentrations than children of parents who disagree with this statement (adjusted difference -103 micromol/L, p < 0.001). Subjective norm: Phe concentrations were higher when parents answered that their relatives did not approve when their child deviates from the diet (p = 0.004). Self-efficacy: children of parents who reported difficulties in having their child eat the synthetic protein substitute three times a day had higher Phe concentrations than those of parents who did not have such difficulties (adjusted difference 156 micromol/L, p = 0.007). CONCLUSION: More attention should be given to parents having their child eat the synthetic protein substitute at least three times a day and to teaching parents to keep strictly to the diet without being too rigid. These factors were strongly associated to dietary control and may be amenable to change.

[Active management of children after ingestion of a button battery]. / Actiefbeleid bij een kind dat een knoopbatterij heeft ingeslikt.

Four children, three girls in the age range up to 14 months and a boy aged 10 years, were admitted because of button battery ingestion. In two patients, the course was uncomplicated, with spontaneous passage of the batteries. Two other patients, a girl aged 11 months and a girl aged 6 weeks, developed severe complications: stenosis of the oesophagus in one patient and a dramatic clinical course with a tracheo-oesophageal fistula and oesophageal damage in the other. Ingestion of foreign bodies in children is a common problem. With the increased use of miniature electronic devices, the incidence of button battery ingestion is rising. Ingestion of a battery is an indication for urgent referral and radiological examination. Electrochemical tissue damage and impaction may lead to serious complications within hours. If the battery is located in the oesophagus, endoscopic removal should be attempted as soon as possible. A conservative approach can be followed when the battery is located in the stomach or beyond, and complaints are absent.

[Icterus prolongatus is a reason for laboratory investigation, also in breastfed neonates]. / Icterus prolongatus reden voor laboratoriumdiagnostiek, ook bij borstgevoede zuigelingen.

Three infants, a boy aged 4 months and two girls aged 3 months and 6 weeks, respectively, had jaundice while they were breastfed. Until then, the jaundice had been interpreted as an innocent consequence of the breastfeeding. In the two eldest patients, however, biliary atresia was diagnosed. A hepatoportoenterostomy was performed in the girl when she was 15 weeks old, but both ultimately underwent a liver transplantation with a good clinical outcome. In the youngest patient, the jaundice disappeared spontaneously and retrospectively was indeed probably associated with breastfeeding. Thorough physical examination and biochemical analyses (total and direct bilirubin, gamma-glutamyl-transferase) are important for the identification of neonatal cholestasis syndromes. Laboratory investigation is recommended in any neonate jaundiced after the age of 3 weeks to differentiate pathological neonatal cholestasis from prolonged jaundice related to breastfeeding.

Tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency in Dutch neonates.

Four neonates with a positive phenylalanine screening test (Phe concentrations between 258 and 1250 micromol/L) were investigated further to differentiate between phenylalanine hydroxylase (PAH) deficiency and variant hyperphenylalaninaemia (HPA) forms. In patients 1 and 2 a tetrahydrobiopterin (BH4) load caused a significant decrease of the plasma Phe levels. A combined phenylalanine/BH4 loading test was performed in patients 2, 3 and 4. In the latter two patients, plasma Phe concentrations completely normalized within 8 h after the BH4 load (20 mg/kg). Basal urinary pterins were normal in all four patients. The activity of dihydropteridine reductase (DHPR) was normal in patients 1, 2 and 3 and 50% of control values in patient 4 (not in the range of DHPR-deficient patients). In patient 3 a subsequent phenylalanine loading test with concomitant analysis of plasma biopterins revealed a normal increase of biopterin, excluding a BH4 biosynthesis defect. Pterins and neurotransmitter metabolites in CSF of patients 1, 3 and 4 were normal. DNA mutations detected in the PAH gene of patients 1-4 were A313T, and L367fsinsC; V190A and R243X; A300S and A403V; R241C and A403V. The results are suggestive for mutant PAH enzymes with decreased affinity for the cofactor BH4.

Phenylketonuria: tyrosine supplementation in phenylalanine-restricted diets.

Treatment of phenylketonuria (PKU) consists of restriction of natural protein and provision of a protein substitute that lacks phenylalanine but is enriched in tyrosine. Large and unexplained differences exist, however, in the tyrosine enrichment of the protein substitutes. Furthermore, some investigators advise providing extra free tyrosine in addition to the tyrosine-enriched protein substitute, especially in the treatment of maternal PKU. In this article, we discuss tyrosine concentrations in blood during low-phenylalanine, tyrosine-enriched diets and the implications of these blood tyrosine concentrations for supplementation with tyrosine. We conclude that the present method of tyrosine supplementation during the day is far from optimal because it does not prevent low blood tyrosine concentrations, especially after an overnight fast, and may result in largely increased blood tyrosine concentrations during the rest of the day. Both high tyrosine enrichment of protein substitutes and extra free tyrosine supplementation may not be as safe as considered at present, especially to the fetus of a woman with PKU. The development of dietary compounds that release tyrosine more slowly could be beneficial. We advocate decreasing the tyrosine content of protein substitutes to approximately 6% by wt (6 g/100 g protein equivalent) at most and not giving extra free tyrosine without knowing the diurnal variations in the blood tyrosine concentration and having biochemical evidence of a tyrosine deficiency. We further advocate that a better daily distribution of the protein substitute be achieved by improving the palatability of these products.

Congenital hepatic fibrosis in 3 siblings with phosphomannose isomerase deficiency.

Congenital hepatic fibrosis is a rare disorder of intrahepatic bile ducts with the persistence of embryological bile duct structures in ductal plate configuration. Three siblings aged 18, 17 and 14 years old were found to have congenital hepatic fibrosis associated with a deficiency of the enzyme phosphomannose isomerase. The clinical symptoms were recurrent attacks of persistent vomiting with diarrhea and mild hepatomegaly. The biochemical abnormalities included elevated serum transferases during attacks, clotting factor deficiencies and persistent hypoalbuminemia. In the youngest patient protein-losing enteropathy was present. Liver biopsies of the three patients taken when they were 1, 3 and 14 years old showed an excess of bile duct structures in ductal plate configuration with mild fibrosis in the portal triads. In one patient the liver biopsy was repeated after 18 years and showed only a mild progression of fibrosis in the portal triads. Duodenal biopsies taken in infancy in two of the three patients did not show any abnormalities. Recognition of phosphomannose isomerase deficiency in association with congenital hepatic fibrosis and protein-losing enteropathy is important, because some of the clinical symptoms are potentially treatable by oral mannose therapy.