Proteomic profiling reveals diagnostic signatures and pathogenic insights in multisystem inflammatory syndrome in children.

Multisystem inflammatory syndrome in children (MIS-C) is a severe disease that emerged during the COVID-19 pandemic. Although recognized as an immune-mediated condition, the pathogenesis remains unresolved. Furthermore, the absence of a diagnostic test can lead to delayed immunotherapy. Using state-of-the-art mass-spectrometry proteomics, assisted by artificial intelligence (AI), we aimed to identify a diagnostic signature for MIS-C and to gain insights into disease mechanisms. We identified a highly specific 4-protein diagnostic signature in children with MIS-C. Furthermore, we identified seven clusters that differed between MIS-C and controls, indicating an interplay between apolipoproteins, immune response proteins, coagulation factors, platelet function, and the complement cascade. These intricate protein patterns indicated MIS-C as an immunometabolic condition with global hypercoagulability. Our findings emphasize the potential of AI-assisted proteomics as a powerful and unbiased tool for assessing disease pathogenesis and suggesting avenues for future interventions and impact on pediatric disease trajectories through early diagnosis.

Host RNA Expression Signatures in Young Infants with Urinary Tract Infection: A Prospective Study.

Early diagnosis of infections in young infants remains a clinical challenge. Young infants are particularly vulnerable to infection, and it is often difficult to clinically distinguish between bacterial and viral infections. Urinary tract infection (UTI) is the most common bacterial infection in young infants, and the incidence of associated bacteremia has decreased in the recent decades. Host RNA expression signatures have shown great promise for distinguishing bacterial from viral infections in young infants. This prospective study included 121 young infants admitted to four pediatric emergency care departments in the capital region of Denmark due to symptoms of infection. We collected whole blood samples and performed differential gene expression analysis. Further, we tested the classification performance of a two-gene host RNA expression signature approaching clinical implementation. Several genes were differentially expressed between young infants with UTI without bacteremia and viral infection. However, limited immunological response was detected in UTI without bacteremia compared to a more pronounced response in viral infection. The performance of the two-gene signature was limited, especially in cases of UTI without bloodstream involvement. Our results indicate a need for further investigation and consideration of UTI in young infants before implementing host RNA expression signatures in clinical practice.

Consequences of COVID-19-related lockdowns and reopenings on emergency hospitalizations in pediatric patients in Denmark during 2020-2021.

There is a considerable burden of children being hospitalized due to infectious diseases worldwide. The COVID-19 pandemic provided a unique opportunity to examine effects of worldwide efforts to control spread of infection. We aimed to investigate overall age-specific hospitalizations due to viral and bacterial infections and diseases triggered by respiratory tract infections during and after lockdown. This nationwide register-based observational study included children from 29 days to 17 years old hospitalized in all Danish pediatric emergency departments during the years 2015-2021. Main outcomes were ICD-10 diagnoses for infectious diseases and infection triggered illnesses. Fluctuations in hospitalization events were explored using figures with weekly events per 100,000. Total events followed a predictable pattern during 2015-2019. In 2020-2021, there was a drop in hospital encounters after lockdowns and surge after reopenings. In 2021, there was a surge of hospital encounters in the late summer due to respiratory syncytial virus infections and asthmatic bronchitis mostly in infants from 29 days to 2 years. For the infectious diseases, there was a dramatic decrease in events after lockdowns and immediate increase in cases that followed the same pattern of previous years after reopenings. Bacterial infections, like urinary tract infections, sepsis, and meningitis followed a steady pattern throughout all calendar-years. CONCLUSIONS: Nationwide efforts to minimize infectious disease spread like lockdowns have a preventative and period lasting effect but reopenings/reunions result in surges of infectious diseases. This might be due to children not getting immunized steadily thereby increasing the pool of possible hosts for potential viral infections. WHAT IS KNOWN: • There is a seasonal fluctuation in viral/respiratory infections in children with higher infection rates in the winter and lower rates in the summer. • RSV infection is a major source of concern. WHAT IS NEW: • Major lockdowns and reopenings disrupt the seasonal fluctuations which can result in high surges in infections that increases the burden of children emergency departments and the risk of serious complications.

Acceptability of Prednisolone in an Open-Label Randomised Cross-Over Study-Focus on Formulation in Children.

Developing acceptable medicines for children is a complicated task. Several factors must be considered, including age, physiology, texture preference, formulation, and legal framework among others. In the development of new paediatric medicines, these factors are assessed. However, for older medicines, e.g., prednisolone, acceptability is still a challenge. This study was an open-label randomised three-arm cross-over study investigating different formulations of prednisolone (crushed tablets, whole tablets, and oral solution) in paediatric patients with asthma and asthma-like symptoms. Participants were randomised into two different formulations on two consecutive days. For each formulation, the child or caregiver was asked to evaluate acceptability using a modified five-point Wong Baker Face scale. An analysis of variance (ANOVA) model was used to test for significance. For the 41 children, included mean age was 4.7 years (SD ± 3.6), and mean weight was 21 kg (SD ± 10.8). Sixty-one percent were boys. The participants were divided accordingly into three age groups: 6 to 23 months (N = 11), 2 to 5 years (N = 14), and 6−11 years (N = 16). The overall acceptability was low, with only 23 out of 71 scores rating the treatment either 1 or 2 (32%). The ANOVA test showed a significant difference in acceptability score between crushed tablets and whole tablets (p < 0.003). The mean acceptability score for the crushed tablet was the least favourable at 3.9 compared to oral solution (3.1), oro-dispersible tablet (2.8), and whole tablets (2.4). This is problematic in long-term treatment and for the youngest children who cannot swallow tablets. The improvement of age-appropriate and acceptable formulations is necessary.

A Retrospective Cohort Study on Infant Respiratory Tract Infection Hospitalizations and Recurrent Wheeze and Asthma Risk: Impact of Respiratory Syncytial Virus.

BACKGROUND: Infant respiratory syncytial virus infection (RSV) has been associated with asthma later in life. We explored the risk of recurrent wheeze or asthma in children with infant RSV-associated hospitalization compared to other respiratory infections. METHODS: We performed a retrospective cohort study using Danish national hospital discharge registers. Infants younger than 6 months, born between January 1995 and October 2018, and with a RSV hospital admission were compared to infants hospitalized for injuries, non-RSV acute upper respiratory tract infection (AURTI), pneumonia and other respiratory pathogens, nonpathogen-coded lower respiratory tract infections (LRTI), pertussis, or nonspecific respiratory infections. Infants were followed until recurrent wheeze or asthma diagnosis, death, migration, age 10 years, or study end. We estimated cumulative incidence rate ratios (CIRR) and hazard ratios (HR) adjusted for sex, age at inclusion, hospital length of stay (LOS), maternal smoking, 5-minute APGAR score (APGAR5), prematurity, and congenital risk factors (CRF). RESULTS: We included 68 130 infants, of whom 20 920 (30.7%) had RSV hospitalization. The cumulative incidence rate of recurrent wheeze or asthma was 16.6 per 1000 person-years after RSV hospitalization, higher than after injury (CIRR, 2.69; 95% confidence interval [CI], 2.48-2.92), AURTI (CIRR, 1.48; 95% CI, 1.34-1.58), or pertussis (CIRR, 2.32; 95% CI, 1.85-2.91), similar to pneumonia and other respiratory pathogens (CIRR, 1.15; 95% CI, .99-1.34) and LRTI (CIRR, 0.79; 95% CI, .60-1.04), but lower than nonspecific respiratory infections (CIRR, 0.79; 95% CI, .73-.87). Adjusted HRs for recurrent wheeze or asthma after RSV hospitalization compared to injuries decreased from 2.37 (95% CI, 2.08-2.70) for 0 to <1 year to 1.23 (95% CI, .88-1.73) for 6 to <10 years for term-born children, and from 1.48 (95% CI, 1.09-2.00) to 0.60 (95% CI, .25-1.43) for preterm-born children. Sex, maternal smoking, LOS, CRF, and APGAR5 were independent risk factors. CONCLUSIONS: Infant RSV hospitalization is associated with recurrent wheeze and asthma hospitalization, predominantly at preschool age. If causal, RSV prophylaxis, including vaccines, may significantly reduce disease burden of wheeze and asthma.

Risk factors for fatigue and impaired function eight months after hospital admission with COVID-19.

INTRODUCTION: We aimed to evaluate post-COVID-19 fatigue, change in functional capacity and health-related quality of life (HRQoL) eight months after discharge from hospital due to COVID-19. METHODS: A total of 83 patients (35 women) admitted to the Copenhagen University Hospital - North Zealand Hospital, Denmark, for COVID-19 during the period from March to June 2020 were evaluated eight months after discharge using validated questionnaires quantifying fatigue, HRQoL and post-COVID-19 functional status. Follow-up data were correlated with measures of pre-COVID-19 status (anthropometrics, comorbidities) and measures of severity of the acute infection. RESULTS: A total of 22 (65%) women and 12 (26%) men reported excessive fatigue. In all, 20 women (67%) and 17 men (37%) reported decreased physical function. Female sex was associated with fatigue. Loss of physical function was associated with pre-COVID-19 presence of heart disease and absence of lung disease. Severity of the acute COVID-19 infection was not associated with fatigue or change in functional status. Fatigue and functional status were correlated with both generic HRQoL and lung disease-specific HRQoL. CONCLUSIONS: Female sex was associated with a higher risk of fatigue eight months after hospitalisation with COVID-19 infection. Regarding loss of functional capacity after COVID-19, we found an apparently protective effect of pre-COVID-19 lung disease. Our findings underscore the urgent need for further research and the importance of evaluating those recovering from COVID-19 for symptoms of excessive fatigue and change in functional capacity irrespective of the severity of the initial infection. FUNDING: none. TRIAL REGISTRATION: not relevant.

Cohort profile: the vitamin A and D and nitric oxide (AD-ON) observational cohort on lung development and symptoms in premature and mature children in North Zealand, Denmark.

PURPOSE: The risk of developing asthma-like symptoms and asthma in childhood is influenced by genetics, environmental exposures, prenatal and early postnatal events, and their interactions. The cohort name refers to vitamins A and D, and nitric oxide (NO) spelt backwards and this cohort profile paper aims to present the data collection and aim of the cohort.The overall aim when establishing this cohort was to investigate if childhood lung function can be traced back to early neonatal lung function and fractional exhaled NO (FeNO) and investigate prenatal and postnatal risk factors including maternal and neonatal vitamin A and D levels in preterm and term born children. PARTICIPANTS: One thousand five hundred women and their babies born at Nordsjaellands Hospital in Denmark from 2013 to 2014 were included in the AD-ON research biobank prior to birth.Neonates from the AD-ON research biobank, admitted to the Neonatal Intensive Care Unit at Nordsjaellands Hospital, were included in the AD-ON neonatal cohort. The neonatal cohort consisted of 149 neonates hereof 63 preterm and 86 term born. The children in the cohort have been invited to follow-up visits at age 1 and 6 years. FINDINGS TO DATE: Published data from this cohort includes a validated and clinically applicable method to measure FeNO in neonates. We found an age-specific pattern of association between respiratory symptoms at age 1 and neonatal FeNO in preterm children. Moreover, we found that the respiratory symptoms risk was associated with postnatal factors (Respiratory Syncytial Virus infection and parental smoking) in preterm infants and prenatal factors (parental asthma and maternal infection during pregnancy) in term born infants. FUTURE PLANS: In the future, the children will be examined continuously with 3-year to 5-year intervals until the age of 18. Lung function, allergy tests, environmental exposure measurements and questionnaires will be collected at each follow-up visit.

Exhaled nitric oxide in premature and mature infants during the first months of life.

AIM: In this review, we aim to describe how exhaled Nitric Oxide(NO) changes during the first months of life in premature and mature infants. METHOD: Review of the literature up to August 2020, on online, tidal breathing NO measurements in unsedated infants. The association between Fractional exhaled NO(FeNO) values, postnatal age, and prematurity was analysed using linear mixed modeling and Spearman's rank correlation. RESULTS: Median FeNO during the first months of life was 5.9 and 8.5 ppb in premature and mature infants, respectively. The linear mixed model analysis showed a significant effect of postnatal age on FeNO (p = 0.007). CONCLUSION: Our study suggests that FeNO is higher in mature infants than premature infants, and FeNO increased with postnatal age at approximately the same pace in both groups.

Characteristics and early outcomes of patients hospitalised for COVID-19 in North Zealand, Denmark.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is an ongoing pandemic associated with significant morbidity and mortality worldwide. Limited data are available describing the clinical presentation and outcomes of hospitalised COVID-19 patients in Europe. METHODS: This was a single-centre retrospective chart review of all patients with COVID-19 admitted to the North Zealand Hospital in Denmark between 1 March and 4 May 2020. Main outcomes include major therapeutic interventions during hospitalisation, such as invasive mechanical ventilation, as well as death. RESULTS: A total of 115 patients were included, including four infants. The median age of adults was 68 years and 40% were female. At admission, 55 (50%) patients had a fever, 29 (26%) had a respiratory rate exceeding 24 breaths/minute, and 78 (70%) received supplemental oxygen. The prevalence of co-infection was 13%. Twenty patients (18%) (median age: 64 years; 15% female) were treated in the intensive care unit. Twelve (10.4%) received invasive mechanical ventilation and three (2.6%) renal replacement therapy. Nine patients (8%) developed pulmonary embolism. Sixteen patients (14%) died. Among patients requiring mechanical ventilation (n = 12), seven (6.1%) were discharged alive, four (3.4%) died and one (0.9%) was still hospitalised. CONCLUSION: In this cohort of hospitalised COVID-19 patients, mortality was lower than in other Danish and European case series. FUNDING: none. TRIAL REGISTRATION: not relevant.

Pharmacokinetics of prednisolone in children: an open-label, randomised, two-treatment cross-over trial investigating the bioequivalence of different prednisolone formulations in children with airway disease.

INTRODUCTION: One in three Danish children under 3 years of age experience asthma-like symptoms, and one-third will later be diagnosed with asthma. Oral prednisolone is used in various formulations to treat acute asthma. However, the potential differences in bioequivalence between these formulations have never been examined in children despite interchangeable use in clinical practice. METHODS AND ANALYSIS: An open-label, randomised, two-treatment cross-over trial investigating the bioequivalence of different prednisolone formulations in children with airway disease.The included patients (6 months-11 years of age) are admitted to the Department of Paediatric and Adolescent Medicine Nordsjællands University Hospital, Hillerød, with asthma or asthma-like symptoms.The primary objective is to assess the bioequivalence between different prednisolone formulations herein area under the concentration time curve, Cmax and Tmax using saliva samples. The secondary objectives are to evaluate tolerability (five-point face scale), adverse events and severity of the disease. If the patient has an intravenous access for other purposes, the saliva samples will be validated with plasma samples.A total of 66 evaluable patients are needed according to European Medicines Agency Guideline on bioequivalence. ETHICS AND DISSEMINATION: Traditional pharmacokinetic trials are burdensome due to the extent of blood samples necessary to capture the time-dependant drug profile. Saliva sampling is far more acceptable for paediatric patients. In addition, this trial adheres to standard dosing strategies. No additional venepunctures are performed, and no additional prednisolone doses are administered.Guidelines for paediatric bioequivalence trials are warranted. TRIAL REGISTRATION NUMBER: The Danish Medicines Agency EudraCT: 2017-003590-33, The Ethics Committee case no: H-17027252, and the Danish Data Protection Agency: BFH-2017-103, I-Suite no.: 05935.

[Mediastinal cystic component as cause of deviating growth in a ten-month-old boy].

We present a case report of a ten-month-old boy, who was referred due to deviating growth and recurrent respiratory tract infections. Computed tomography of the thorax showed two large, cystic components in the mediastinum. He underwent surgical removal of the cysts. Pathological examination confirmed the diagnosis lymphatic malformation. This case illustrates that intrathoracic tumors such as lymphatic malformations, although rare, should be considered in children with deviating growth curves and respiratory problems. Rather than continuous symptomatic treatment children with symptoms early in life should be prompted in further investigations.

Clinical manifestations in infants and children with Mycoplasma pneumoniae infection.

BACKGROUND: Mycoplasma pneumoniae is a common cause of community-acquired pneumonia in older children. Pulmonary and extra-pulmonary symptoms associated with M. pneumoniae infection are reported. M. pneumoniae is mainly epidemic in Denmark with the recurrence every 4-7th year. AIMS: Retrospectively, to describe the epidemiology and clinical features, in infants and children, during the M. pneumoniae epidemic in 2010 and 2011. METHODS: All children under the age of 16 that were tested for M. pneumoniae during the period 01.02.2010-31.01.2012 were included. Medical charts, as well as radiological findings, were reviewed for all children with M. pneumoniae. A post-hoc analysis of viral co-infections was done on part of the cohort. RESULTS: 134 of 746 children were tested positive for M. pneumoniae by PCR or serology. Positive tests were found in 65% of children seven years and older, in 30% of 2-6-year-olds and 4% of infants (less than two years of age). Viral co-infection was found in 27% of the tested samples. The clinical presentation was a cough, asthma-like symptoms and low-grade fever. Extra-pulmonary symptoms were common and presented as nausea/vomiting by 33% of the children and skin manifestations by 25%. 84% of the children had a chest x-ray taken, and there were positive radiological findings in 94% of these. CONCLUSION: M. pneumoniae also affected infants and young children and symptoms were similar to infections with respiratory viruses, but severe LRTI were also seen. During an up-coming epidemic, assessment of extra-pulmonary manifestations can be helpful when diagnosing M. pneumoniae infections.

[Acupuncture-induced bilateral pneumothorax in a 16-year-old boy].

Acupuncture is a well-known form of alternative medicine, it is becoming increasingly popular in Denmark for a wide variety of uses, and is also practiced on children. However, there is a risk of serious complications. This is a case report of acupuncture-induced bilateral pneumothorax in a 16-year-old boy, who had been admitted to the emergency department with chest pain. Treatment included a unilateral chest tube in the left lung and conservative treatment in the right lung. Physicians must be aware of pneumothorax as a serious complication of acupuncture in the thoracic region.

A new model of paired clinical teaching of international and Danish medical students.

INTRODUCTION: Since 2006, one hospital has offered two clinical courses in obstetrics/gynaecology and paediatrics to international (I) students. However, as I-student enrolment increased, the hospital faced cut-backs. As from 2010, I-team course evaluations therefore dropped to unacceptable levels and more I- than Danish (DK) students failed exams. Therefore, in 2012 we started a three-year internationalisation project (I-project) at two hospitals. The primary intervention was to pair training for I- and DK-students at clinical contact, and to offer an exclusive daily lecturer for I-teams. METHODS: We compared the course evaluations and exam grades of I-teams and DK-teams for two years prior to (107 from I-teams - 211 participants from DK-teams) and during the I-project (245 participants from I-teams - 575 from DK-teams). RESULTS: During the I-project, the I-teams' course evaluations increased to acceptable values and to levels comparable to the evaluation scores of DK-teams. Furthermore, I-students now considered that their communication with the patients was acceptable. Before the I-project, I-students had lower exam grades (median = 10 (range: 0-12)) than DK-students (10 (4-12)) (p = 0.03), but during the I-project, exam grades increased to the levels achieved by DK-students (10 (2-12) - 10 (0-12) (p = 0.22), and no more I- than DK-students failed exams (p = 0.51). CONCLUSIONS: Pairing students for clinical training and allocating an exclusive lecturer for I-teams produced improved courses for internationalisation. Allocating an exclusive lecturer was associated with a cost of about 615 EUR per student per course when the team consisted of ten students. FUNDING: The Capital Region of Denmark and the University of Copenhagen. TRIAL REGISTRATION: not relevant.

MMR vaccination of children with egg allergy is safe.

INTRODUCTION: Measles, mumps and rubella (MMR) vaccination is part of the Danish Childhood Vaccination Programme. It is known that children may react with anaphylaxis to MMR vaccines containing traces of egg protein. In Denmark, national clinical guidelines recommend that children with egg allergy be referred to vaccination at a paediatric ward despite changed recommendations in other countries. The purpose of this study was to determine whether children with egg allergy presented with anaphylactic/allergic reactions to MMR vaccination and to discuss whether Danish recommendations should be upheld. MATERIAL AND METHODS: Data collected through evaluation of the histories of children referred to the Paediatric Ward at Hillerød Hospital from 01.01.2008 to 28.02.2011 and coded according to action diagnosis and/or supplementary diagnosis in International Classification of Diseases 10 (ICD-10) for food allergy, oedema angioneurotica and tentative diagnosis as well as the procedure code for oral food challenge. A total of 32 patients were included, all were both sensitized to egg and had been MMR vaccinated. RESULTS: The 32 patients had received a total of 41 doses of MMR vaccine. None of them had shown anaphylactic/allergic reactions to the MMR vaccines. 23% of the vaccines were given with considerable delay. CONCLUSION: Based on our study, we conclude that the Priorix MMR vaccine may be administered just as safely to children diagnosed with egg allergy as to other children. We found no evidence in support of the current Danish recommendations. We therefore recommend that the Statens Serum Institut, the Danish Paediatric Society and/or the Danish Health and Medicines Authority reconsider these recommendations. FUNDING: not relevant TRIAL REGISTRATION: not relevant.

Bone mineral status in children with cow milk allergy.

To investigate bone mineral status in children with verified cow milk allergy for more than 4 yr compared with a large reference population of 343 local healthy controls. Whole body bone mineral content (BMC), projected bone area and bone mineral density (BMD) were determined by dual energy x-ray absorptiometry in nine children (8-17 yr old, one girl and eight boys). All children had cow milk allergy for more than 4 yr. All children had asthma and was treated with corticosteroids. BMC and BMD were reduced for age (p < 0.01). Height for age was significantly reduced (p < 0.01), indicating 'short' bones. BMC for bone area was borderline reduced (p = 0.05), indicating reduced bone mineralization. The growth of the children was reduced compared with there parents and siblings (p < 0.01), and the bone age was retarded (mean 1.4 yr, p < 0.01). Calcium consumption calculated from food intake was about 25% of the recommended. All laboratory tests were normal. Short bones were the main reason for reduced BMC and BMD for age in children with cow milk allergy, but a borderline low BMC for bone area indicated reduced bone mineralization of the bones. A supplementation of calcium to children with cow milk allergy is recommended.

Epidemic spread of Pandoraea apista, a new pathogen causing severe lung disease in cystic fibrosis patients.

We show that Pandoraea apista must be added to the increasing list of pathogens capable of causing chronic lung infection in cystic fibrosis (CF) patients. It is most likely that this strain of P. apista was transmissible among patients with CF, leading to spread of infection from the index patient to 5 other patients exposed during participation in winter camps and/or hospitalization. All patients developed chronic infection with high levels of antibodies, and 4 patients had a downhill course of lung disease. P. apista must therefore be considered a new and sometimes important pathogen for CF patients. Cohort isolation prevented further spread of P. apista in our CF center.

Asthma mortality in the Danish child population: risk factors and causes of asthma death.

Child death due to asthma is a rare and potentially preventable event. We investigated possible risk factors for death due to asthma in children and adolescents, as a step towards preventing or minimizing asthma death in this age group, and improving asthma management and care. We reviewed all 108 cases of asthma death in 1-19-year-olds in Denmark, 1973-1994. Copies of death certificates, hospital records, information from general practitioners, and autopsy records were obtained. The information was assessed with particular reference to: features and duration of asthma before death; severity of asthma; time and place of death; long-term and ongoing medical treatment; quality of medical care; circumstances of final illness; and medical treatment during the final episode of asthma. Age groups of 1-4 years, 5-14 years, and 15-19 years were analyzed separately and in aggregate. Death occurred predominantly in the 15-19-year age group. Generally, significantly more patients died in the summer. These patients were more atopic, had fewer asthma symptoms, and did not have regular asthma consultations. Nearly all patients had early-onset asthma. The 1-4-year age group was characterized by severe asthma. Major risk factors (all age groups) were: gradual deterioration during the last month; length of final attack (>3 hr); and delay in seeking medical help during the final attack. None of the children died during their first attack. Nonadherence was most frequent among the 15-19-year-olds. All asthmatic children and young adults should regularly receive medical care and assessment, even if they suffer only a few symptoms. This study underlines the need for ongoing education of the patient's family, the patient, and doctors on long-term management and management of acute attacks. Copies of clearly written individual plans for periods with increasing symptoms should be supplied to the patient/family and, where appropriate, to their general practitioners. The object of these measures is that the patient and parents/family learn to recognize the signs of deterioration and to act on them.

The prevalence of latex sensitisation and allergy in Danish atopic children. Evaluation of diagnostic methods.

BACKGROUND: All over the world natural rubber allergy is reported to be responsible for a wide spectrum of allergic symptoms ranging from mild rhinitis to severe anaphylaxis. AIM: To estimate the prevalence and the clinical significance of latex sensitisation in atopic children seen in a university paediatric outpatient clinic. MATERIALS AND METHODS: During 1997-1998, a total of one hundred atopic children (4-14 years old, 64 boys and 36 girls) were consecutively screened for latex sensitisation by skin prick tests (SPTs) with standard inhalant allergens (ALK) and latex (Stallergenes SA), measurement of specific IgE (CAP System, Pharmacia, and Magic Lite, ALK) and total IgE. A clinical history with attention to surgical history, latex exposure and presence of symptoms possibly due to latex or food allergy was obtained. RESULTS: Five children (5%) had positive SPT to latex. Four (4%) had positive specific IgE to latex but had a negative SPT to latex. Only one patient (1%), who had spina bifida, had a positive SPT together with symptoms which could be related to latex allergy. This patient also had RAST class 4 to latex both with CAP System and Magic Lite. A history of previous surgery was found in only one of the children with positive latex SPT. Latex CAP System was positive in two of the five latex SPT positive patients, and latex Magic Lite in one of the five. In one patient without any symptoms of latex allergy, both SPT and in vitro tests were positive. Another child without symptoms, and with negative SPT, also had positive in vitro results. CONCLUSION: We found that the prevalence of sensitisation to latex was 9% in atopic children, but the prevalence of manifest type 1 latex allergy was only 1%. Latex allergy in atopic children seems to be a small problem in Denmark. How to evaluate the significance of positive in vitro tests and positive latex SPT in patients without symptoms to latex, remains an open question.