Gastrointestinal Symptoms of Food Challenge-proven Non-IgE Cow's Milk Allergy Are Dissipated by Early School Age.

OBJECTIVES: The aim of this study was to evaluate the current well-being and dietary restrictions in children 6 years after food challenge-confirmed diagnosis of non-IgE cow's milk protein allergy, compared to peers with gastrointestinal symptoms but negative food challenge. This study aimed to evaluate the diagnostic process retrospectively. METHODS: This is an Internet-based survey for mothers whose children underwent 6 years ago the double-blind, placebo-controlled food challenge for cow's milk (CM) because of gastrointestinal symptoms causing suspicion of non-IgE CM protein allergy. Concurrent dietary restrictions, overall well-being, medical history, and retrospective views on the food challenge were queried using a study-specific questionnaire, the Quality of life using PedsQL general score and parental stress with the Parenting Stress Index questionnaire. RESULT: Mothers of 42 children (23 girls), median age of 6.7 years (range 5.7-8.6), participated in the survey, the response rate was 70%. All children now consumed cow's milk protein. The only food restrictions reported were empirical lactose-free diets in 7 children (17%). One-third of the children in both groups were presently reported to have eating-related issues such as picky eating. Quality of life was good and present parenting stress was average in both groups. The majority of the mothers (87%) felt positive or neutral about the food challenge performed in infancy. CONCLUSIONS: The non-IgE CM allergy with gastrointestinal symptoms diagnosed in infancy was a transient condition with good outcome. At an early school age, nearly all children have a good quality of life and a regular diet. The use of the double-blind, placebo-controlled food challenge was well-endorsed.

Blood pressure profiles 5 to 10 years after transplant in pediatric solid organ recipients.

Arterial hypertension is a major risk factor for cardiovascular disease after solid organ transplantation, emphasizing the need for blood pressure (BP) monitoring. The authors studied 24-hour ambulatory BP monitoring (ABPM) parameters (index, load, dipping) and their predictive value with regard to hypertension as well as correlations with graft function and metabolic parameters such as obesity and dyslipidemias. The ABPM profiles of 111 renal, 29 heart, and 13 liver transplant recipients were retrospectively analyzed 5 to 10 years after transplant (median 5.1 years). The BP profiles among the different transplant groups were similar. The BP index and load were abnormal especially at nighttime and the nocturnal BP dipping was often blunted (in 49% to 83% of the patients). The BP variables were found to be equally valued when assessing hypertension. BP load of 50% instead of 25% seems to be a more adequate cutoff value. The BP variables correlated poorly with the metabolic parameters and kidney function. Antihypertensive medication did not notably change the ABPM profile in renal transplant recipients. Hypertension, including nocturnal hypertension, is present in children receiving solid organ transplant, underlining the importance of use of ABPM in the follow-up of these patients.

Diagnosis and treatment of bronchiolitis in Finnish and Swedish children's hospitals.

AIM: There is no widely accepted consensus on the diagnosis and treatment of bronchiolitis. This study describes current practices in Finnish and Swedish hospitals. METHODS: A questionnaire on the diagnosis and treatment of bronchiolitis in children below 2 years of age was sent to all Finnish and Swedish hospitals providing inpatient care for children. All 22 Finnish hospitals answered, covering 100% of the <12-month-old population and 21 of the 37 Swedish hospitals responded, covering 74%. RESULTS: The mean upper age limit for bronchiolitis was 12.7 months in Finnish hospitals and 12.5 months in Swedish hospitals. In both, laboured breathing, chest retractions and fine crackles were highlighted as the main clinical findings, followed by prolonged expiration. The mean value for the lowest acceptable saturation in room air was 94% in Finnish hospitals and 93% in Swedish hospitals. The most important factors influencing hospitalisation were young age, desaturation and inability to take oral fluids. Finnish doctors preferred intravenous routes, and Swedish doctors preferred nasogastric tubes for supplementary feeding. The first-line drug therapy was inhaled racemic adrenaline in Finland and inhaled levo-adrenaline in Sweden. CONCLUSION: The diagnosis and treatment of bronchiolitis is fairly similar in Finnish and Swedish hospitals.

Metabolic risk factors and long-term graft function after paediatric renal transplantation.

The aim of this study was to evaluate metabolic risk factors and their impact on long-term allograft function in paediatric renal transplant (RTx) patients. We reviewed the medical records of 210 RTx patients who underwent transplantation at a median age of 4.5 years (range 0.7-18.2) and a median follow-up of 7.0 years (range 1.5-18.0). Data on lipid and glucose metabolism, uric acid levels, weight and blood pressure were collected up to 13 years post-RTx, and the findings were correlated with the measured glomerular filtration rate (GFR). Beyond the first year, GFR showed gradual deterioration with a mean decline of 2.4 ml/min/1.73 m(2)/year. Metabolic syndrome, overweight, hypertension and type 2 diabetes were diagnosed in 14-19%, 20-23%, 62-87% and 3-5% of the patients, respectively. These entities showed only mild association with the concomitant or long-term GFR values. Dyslipidaemia was common and hypertriglyceridaemia associated with a lower GFR at 1.5 and 5 years post-RTx (P = 0.008 and P = 0.017, respectively). Similarly, hyperuricaemia was frequent and associated significantly with GFR (P < 0.001). Except for hyperuricaemia and hypertriglyceridaemia, metabolic risk factors beyond the first postoperative year associated modestly with the long-term kidney graft function in paediatric RTx patients.

A time-to-event model for acute rejections in paediatric renal transplant recipients treated with ciclosporin A.

AIMS: Ciclosporin A (CsA) dosing in immunosuppression after paediatric kidney transplantation remains challenging, and appropriate target CsA exposures (AUCs) are controversial. This study aimed to develop a time-to-first-acute rejection (AR) model and to explore predictive factors for therapy outcome. METHODS: Patient records at the Children's Hospital in Helsinki, Finland, were analysed. A parametric survival model in NONMEM was used to describe the time to first AR. The influences of AUC and other covariates were explored using stepwise covariate modelling, bootstrap-stepwise covariate modelling and cross-validated stepwise covariate modelling. The clinical relevance of the effects was assessed with the time at which 90% of the patients were AR free (t90). RESULTS: Data from 87 patients (0.7-19.8 years old, 54 experiencing an AR) were analysed. The baseline hazard was described with a function changing in steps over time. No statistically significant covariate effects were identified, a finding substantiated by all methods used. Thus, within the observed AUC range (90% interval 1.13-8.40 h mg l⁻¹), a rise in AUC was not found to increase protection from AR. Dialysis time, sex and baseline weight were potential covariates, but the predicted clinical relevance of their effects was low. For the strongest covariate, dialysis time, median t90 was 5.8 days (90% confidence interval 5.1-6.8) for long dialysis times (90th percentile) and 7.4 days (6.4-11.7) for short dialysis times (10th percentile). CONCLUSIONS: A survival model with discrete time-varying hazards described the data. Within the observed range, AUC was not identified as a covariate. This feedback on clinical practice may help to avoid unnecessarily high CsA dosing in children.

Risk factors for impaired quality of life and psychosocial adjustment after pediatric heart, kidney, and liver transplantation.

Few studies compare HRQOL and PSA in children who have undergone different types of solid organ Tx. In this cross-sectional study, HRQOL and PSA were assessed in 74 Tx patients (16 heart, 44 kidney, 14 liver) at a mean age of 11.5 (range 6.3-16.7), 7.2 yr post-Tx (range 1.0-15.0). HRQOL was self-assessed using standardized health utility questionnaires (15D-17D). The patients' PSA was evaluated using the Child Behavior Checklist for parents, Youth Self-Report for patients aged 11-16 yr, and Teacher Report Form. Outcomes did not differ significantly between Tx groups. Preadolescents (8-11 yr) reported poorer HRQOL compared with same-age peers (p = 0.020). In contrast, adolescents reported similar HRQOL and PSA compared to the general population. Proxy-reports revealed more PSA problems compared with age expectations (p < 0.01), mainly in internalizing behavior (p < 0.01). Lower HRQOL was associated with shorter follow-up time since Tx, congenital disease, and a psychiatric or neurological diagnosis. PSA problems were associated with family-related variables, neurological diagnosis, shorter follow-up time, and in teacher-reports longer disease duration before Tx. Different pediatric Tx groups have similar outcome. Neurological comorbidity and shorter follow-up time are important risk factors, but the impact of family-related variables on PSA indicate the need of family interventions.

[Evaluation of training of pediatric specialists]. / Lastentautien erikoislääkäri--koulutuksen arviointi.

Regular audit of training of specialist physicians by means of comparable methods is a recommended means to take care of immediate quality assessment of the training. An audit group consisting of the professor of pediatrics at the University of Helsinki and professor of pediatrics at the University of Tampere, two clinical lecturers and two representatives of physicians specializing in pediatrics at the Children's Hospital together with an outside expert evaluates the common trunk belonging to specialization in pediatrics in teaching hospitals. The group stated that the recommendation for degree associated with specialist training is being followed in the hospitals, but the follow-up of the objectives and their implementation is insufficient.

Outcome of pediatric heart transplantation recipients treated with ventricular assist device.

This study was conducted to evaluate the long-term prognosis of pediatric HTx patients treated with VAD before transplantation. The clinical data of six patients bridged to HTx with Berlin Heart EXCOR pediatric device were analyzed retrospectively. Information about graft function, CA results, and EMB findings as well as appearance DSA was collected. Also, information about growth and cognitive function was analyzed. These findings were compared with age-, gender-, and diagnosis-matched HTx patients. During the median follow-up time of four and half yr after HTx, the prognosis including graft function, number of rejection episodes, and incidence of coronary artery vasculopathy, growth and cognitive development did not differ between VAD-bridged HTx patients compared with control patients. In both groups, one patient developed positive DSA titer after HTx. Our single-center experience suggests that the prognosis of pediatric HTx patients treated with VAD before transplantation is not inferior to that of other HTx patients.

Neuropsychological profile of children with kidney transplants.

BACKGROUND: Varying results on the cognitive outcome of children who have undergone kidney transplantation (KTx) have raised concern for specific neurocognitive difficulties. METHODS: Fifty children with KTx were assessed at a mean age of 11.1 (SD 3.2; range 6.3-16.4), on average 6.9 (SD 3.6; range 1.0-14.1) years post-operatively. A standardized test of intelligence [Wechsler Intelligence Scale for Children (WISC-III)] and neuropsychological tests from NEPSY-II were administered. The neuropsychological profile of KTx children was compared to that of a control group matched for gender, age and maternal education. RESULTS: The KTx children had a lower intelligence quotient (83.9) than the test norms (100.0, P < 0.001). On neuropsychological assessment, the KTx group scored generally lower than the control group did (P < 0.001). The difference was evident in both the verbal and visuospatial domains, on a sub-test of complex auditory attention, verbal working memory and facial affect recognition. When children with neurological co-morbidity were excluded, the remaining group still scored lower than the controls did on Comprehension of Instructions (P = 0.06), Design Copying (P = 0.007) and Affect Recognition (P = 0.018). A better cognitive outcome was mainly associated with the absence of neurological co-morbidity, younger age, shorter disease duration and sustained kidney function. Children with congenital nephrosis had a similar outcome to those with other diagnoses. CONCLUSIONS: KTx children exhibit a pattern of effects in their cognitive outcome in which both the visuospatial and language domains are affected, but visual memory and simple auditory attention remain intact. Patients without neurological co-morbidity exhibit impairment in receptive language, visuospatial functions and in recognizing emotional states.

Donor-specific HLA antibodies and graft function in children after renal transplantation.

BACKGROUND: The presence of circulating donor-specific human leukocyte antigen antibodies (HLA-DSA) has been associated with chronic antibody-mediated rejection, leading to progressive graft dysfunction and poor graft survival.The aim of this study was to investigate the incidence and significance of HLA-DSA in paediatric renal transplantation(RTx) patients. METHODS: A total of 294 post-transplant serum samples from 123 RTx patients were retrospectively analysed for HLA antibodies. Positive samples were further tested for HLADSA by a Luminex Single Antigen bead assay. The antibody findings were correlated to measured glomerular filtration rate(GFR) and clinical outcome. RESULTS: HLA antibodies were detected in half of the routine samples (140/294) taken 1 month to 10 years after RTx, and 40% (62/140) of these were HLA-DSA. Overall, one-third(42/123) of the patients had HLA-DSA, which mostly(65%) reacted against class II antigens. Detection of HLADSA was not associated with poor GFR at the time of sampling, and no exceptional deterioration of GFR after the HLA-DSA detection was noted in individual patients regardless of the antibody level. The presence of HLA-DSA in the first 2 years posttransplantation was not associated with poorer graft function later on. CONCLUSION: Detection of HLA antibodies is common in children after RTx, and this finding, as such, does not predict any deterioration of graft function.

Quality of life in adult survivors of pediatric kidney transplantation.

BACKGROUND: There are few studies assessing long-term adult outcome and health-related quality of life (HRQOL) in former pediatric high-risk kidney transplant (TX) recipients. METHODS: Twenty-one patients were assessed at mean age of 21.1 years. Mean age at first TX was 2.4 years. Brain arterial border zone infarcts had been documented in 54% of the children. HRQOL was assessed with the general 15-dimensional (15D) instrument generating an index on a 0 and 1 scale (1 for best). The results were compared with the corresponding childhood 17-dimensional instrument and an adult control group from the general population. Psychosocial adjustment was assessed with the ASEBA Adult Self Report (ASR) and compared with the childhood Child Behavior Checklist assessments. RESULTS: Half of the patients (52%) had a secondary level general or vocational education. The educational outcome was evenly distributed (compulsory vs. secondary) regardless of previous childhood brain ischemia. The ASR Total Problems score was in the normal range for all patients. Four patients had scores in the pathological range for Externalizing or Internalizing Problems. There was a correlation between the childhood Child Behavior Checklist problem scores and the adult ASR scores for Internalizing and Total Problems but not for Externalizing Problems. Their mean 15D HRQOL index was 0.94 and lower than for the control group (0.97, P=0.04). There was a strong correlation between the childhood 17-dimensional and the adult 15D HRQOL index (r=0.63, P=0.003). CONCLUSION: The long-term outcome is fair in former high-risk pediatric TX patients with neurological comorbidity. Childhood psychosocial adjustment and HRQOL may predict the outcome in adults.

Pubertal development is normal in adolescents after renal transplantation in childhood.

BACKGROUND: This study was conducted to evaluate the pubertal development in adolescents after renal transplantation (RTx) in childhood. METHODS: We performed a retrospective review of medical records of 109 RTx recipients (72 males) transplanted at the median age of 4.5 years (range: 0.9-15.8 years). Data on the clinical signs of puberty, growth, bone age, medication, and graft function of 98 patients were analyzed. Furthermore, serum levels of reproductive hormones in 87 patients were assessed to evaluate the progression and outcome of pubertal development. RESULTS: The age at the onset of puberty averaged 12.7 years (range: 9.4-16.2 years) in 55 males and 10.7 years (range: 8.9-12.7 years) in 29 females. The mean age at menarche was 12.5 years (range: 10.5-14.5 years). Twenty-two percent of the boys and none of the girls had a moderately delayed onset of puberty. Children who underwent RTx before the age of 5 years reached puberty earlier than those transplanted at later age (boys 12.3±1.2 vs. 13.4±1.5 years, P<0.01; girls 10.3±0.9 vs. 11.0±1.0 years, P>0.05). The mean length of puberty was 3.9 and 4.7 years for boys and girls, respectively. The bone age was delayed in practically all, and final height was reached at the mean age of 18.1 and 16.0 years in boys and girls, respectively. Pubertal maturation resulted in acceptable final height and reproductive hormone status in great majority of the patients. CONCLUSION: Pubertal development was normal in all female and most male adolescents after RTx in childhood.

Visuospatial impairment in children and adolescents after liver transplantation.

A minority of children with liver transplants exhibit significant delay in global intelligence; others have specific learning disabilities. More specific data on neurocognitive strengths and weaknesses are lacking. Eighteen children aged 7-16 yr, who had undergone LTx in Finland participated in the study. They were assessed on an average 7.6 (s.d. 4.5, range 1.0-15.0) years post-operatively at a mean age of 11.8 (s.d. 3.1, range 7.2-16.1). A standardized test of intelligence (WISC-III), a neuropsychological test battery (NEPSY-II), and a parental questionnaire on the child's development (FTF) were administered. The neuropsychological test profile of the LTx group was compared with that of a matched control group of healthy children. The LTx children achieved on an average normal FSIQ 94.0 and VIQ 99.6. Their Performance Intelligence Quotient (PIQ 88.9, p=0.043) was, however, significantly lower than the population mean. On neuropsychological assessment, the LTx children scored generally lower than the control group (p=0.004), a difference significant in sub-tests assessing visuospatial and visuoconstructive functions and social perception. No differences emerged in sub-tests of attention and executive functions, memory and learning, or language functions. LTx children are at increased risk for impairment in the visuospatial domain.

Neurocognitive function of pediatric heart transplant recipients.

BACKGROUND: Pediatric heart transplant recipients exhibit cognitive delays, as evident in assessments of their general intelligence. Less is known about their specific neurocognitive impairments. METHODS: All 19 children in Finland aged 6 to 16 years who had undergone heart transplantation (HTx) participated. Of these, 12 (63%) had cardiomyopathy (CM) and 7 (37%) had congenital heart disease (CHD). They were assessed on average 5.5 (SD, 3.6) years post-operatively at a mean age of 12.0 (SD, 3.1) years. A standardized test of intelligence (Wechsler Intelligence Scale for Children [WISC]-III), a neuropsychological test battery (NEPSY-II), and a parental developmental questionnaire (FTF) were administered. The neuropsychological test profile of the HTx group was compared with that of a matched control group. RESULTS: HTx children had a lower mean Performance Intelligence Quotient (PIQ; 82.2, p = 0.001) and Full-Scale IQ (FSIQ; 85.6, p = 0.004) compared with population norms. HTx children scored generally lower than the control group on the neuropsychological tests (p = 0.002). Seven patients with pre-HTx neurologic sequelae (n = 6) or extreme prematurity (n = 1) had lower mean FSIQ (72.1) than did children without major pre-HTx risk factors (93.5, p = 0.012). The latter group scored below average on only 1 of 6 WISC-III sub-tests and 2 of 10 NEPSY-II sub-tests, all measuring visuoconstructional performance. CONCLUSIONS: Children without major neurologic risk factors pre-HTx may have normal general intelligence after HTx but deficits in the visuoconstructional domain.

[An infant less than three months of age at emergency call service]. / Alle kolmen kuukauden ikäinen lapsi päivystyksessä.

Examination and treatment of an infant less than three months of age requires different action at the emergency department as compared with bigger children. Even slight cough and vomiting may be indications of a severe disease in this age group. In addition, symptoms in small infants are often diffuse and sometimes difficult to observe and analyze. A general assessment by the physician constitutes the basis for diagnostics. Of the severe diseases, most are infections.

Headache in children and adolescents after organ transplantation.

The prevalence and characteristics of headache were studied in a national cohort of 177 pediatric patients with kidney, liver, and heart transplants. All patients received triple drug immunosuppression with CsA, Aza, and MP. Data on headaches were collected by sending two questionnaires and reviewing the medical records. Statements on headache were found in the medical records of 46% of the patients. According to a questionnaire, two thirds had experienced headaches sometime after transplantation, and 40% had present headaches. The episodes had significantly affected the quality of life in a third of the patients, and resulted in neurological examination in 15%. Most of the subjects (61%) described typical episode as mild or moderate, and 39% as severe or very severe. The usual episodes lasted <4 h in 73% of the patients and >4 h in 27%. The headache could be classified as migraine, probable migraine or headache without specific features in 33%, 31%, and 36%, respectively. Most patients (82%) had used pain-killers, mainly acetaminophen and ibuprofen. Headache episodes may significantly impair the quality of life in children and adolescents after organ transplantation.

Early treatment of acute rejections gives favorable long-term function after renal transplantation in small children.

AR is considered as a risk factor for CAN after kidney TX. We combined data on AR with long-term graft function and histopathology to assess whether early treatment of AR is beneficial for long-term graft outcome in small children. Seventy-seven children with a mean age of 4.7 yr were studied. Early AR were diagnosed with FNAB and treated with methylprednisolone already before clinical signs occurred. The children were grouped into three groups (clinical, subclinical, and no AR) and then followed prospectively up to seven yr after TX with measured GFR and core needle biopsies to assess histopathological findings with the CADI score. Early AR, whether clinical or subclinical, did not affect long-term graft survival (80% with AR vs. 83% without AR, at 10 yr). Late AR, more than one yr after TX, had an inferior graft survival 50% vs. 84% (p = 0.02). GFR declined and the CADI scores increased with time, but there were no significant differences between the three groups. Prompt and early treatment of post-operative AR gives favorable long-term graft function compared with children without AR. Late AR is a risk factor for inferior long-term graft function.

Plasma exchange and retransplantation in recurrent nephrosis of patients with congenital nephrotic syndrome of the Finnish type (NPHS1).

BACKGROUND: Recurrent nephrotic syndrome (NS) is a severe problem after renal transplantation in patients with congenital nephrotic syndrome of the Finnish type (NPHS1). The NPHS1 kidneys do not express nephrin, and antibodies against this major glomerular filter protein have been observed in NPHS1 children with recurrent NS. We evaluated here the use of plasma exchange (PE) therapy and kidney retransplantation in NPHS1 patients with recurrent NS and extended our studies on the pathogenesis of the recurrence. METHODS: Clinical data on 65 NPHS1 patients who received 77 kidney transplants between the years 1986 and 2006 was collected. Serum anti-nephrin antibodies were assayed with an enzyme-linked immunosorbent assay method, and the kidney biopsy samples were evaluated by light microscopy and immunohistochemistry. RESULTS: Twenty-three episodes of recurrent NS occurred in 19 grafts of 13 NPSH1 patients homozygous for Fin-major mutation. Six retransplantations were performed to four NPHS1 patients, who lost their graft because of recurrent NS, and heavy proteinuria developed immediately in all cases. Although 73% of the patients had detectable serum anti-nephrin antibodies, the kidney biopsy findings were minimal. Introduction of PE alongside cyclophosphamide proved effective in the treatment of the proteinuric episodes (one graft loss out of nine). If remission was achieved, recurrent NS did not significantly deteriorate the long term graft function. CONCLUSIONS: The clinical and pathological data suggest that anti-nephrin antibodies effectively impair the glomerular function in kidney grafts of NPHS1 patients homozygous for Fin-major mutation. Plasma exchange is a useful adjunct to the treatment of the recurrent NS.

Muscular dystonia and athetosis in six patients with congenital nephrotic syndrome of the Finnish type (NPHS1).

Congenital nephrotic syndrome of the Finnish type (NPHS1, CNF) is an autosomal recessively inherited disease occurring due to mutations in the nephrin gene (NPHS1). Two main Finnish mutations exist: Fin-major and minor, which both cause a lack of nephrin and absence of the slit diaphragm between the podocytes. This leads to severe proteinuria, nephrotic syndrome and infections, and without dialysis or renal transplantation, death in infancy. Between 1984 and 2003, six (8.6%) of the 70 NPHS1 patients diagnosed at our institution had, in addition to their renal disease, similar neurological symptoms. All six showed a severe dyskinetic cerebral palsy-like syndrome with dystonic features, athetosis and a hearing defect. The neurological symptoms became apparent during their 1st year of life and were diagnosed before 11 months of age. MRI showed increased signal intensity in T2-weighted images in the globus pallidus area. No mitochondrial gene mutations explaining the neurological symptoms were found, nor did external neurological complications explain them when compared with 29 NPHS1 control patients. Four children died at an early age: two during dialysis and two shortly after renal transplantation. Two are still alive with a functioning graft. Both have severe motor defects, but are mentally active and social.