Rasmus Gaardskær Nielsen

Use of complementary/alternative medicine among paediatric patients

The use of complementary/alternative medicine (CAM) is increasing. The aim was to characterise the use of CAM among patients in a paediatric department. All patients (aged 0-18 years), out-patients or hospitalised, in contact with the Department of Paediatrics, Odense University Hospital during a 2 week period in the autumn of 2001 were asked to participate. In total, 622 (92%) patients participated. The data were collected in an interviewer administered questionnaire during a short structured interview with the patient and parents. CAM was divided into herbal medicine (herbal drugs or dietary supplements) (HM), alternative therapy (AT) (i.e. acupuncture) or chiropractic (CHI). Of all patients, 53% had tried CAM at least once and 23% had tried CAM within the last month (15% HM, 7% AT and 2% CHI). There was no correlation between use of CAM and gender, age or if the patient was out-patient or hospitalised. The users were pre-school children. HM (Bio-Strath and Echinacea) was especially used to strengthen the immune system. Among AT, reflexological treatment was the most popular treatment. The most frequent users of CAM were patients with asthma, eczema or allergy plus patients suffering from gastrointestinal diseases or hospitalised for observation. More than 50% of the users experienced positive effects and 6% had side-effects from AM. Of the CAM users, 11% or 2% of the total paediatric population used CAM instead of conventional medicines. Conclusion: Of the paediatric patients, 53% had tried complementary/alternative medicine, which was used as a supplement to conventional medicine although we did not know how long it was used. Paediatric patients should be interviewed about their use of complementary/alternative medicine with regard to side-effects, interactions or lack of compliance with conventional medicine.

Severe gastroesophageal reflux disease and cow milk hypersensitivity in infants and children: disease association and evaluation of a new challenge procedure.

Background: Gastroesophageal reflux disease (GERD) and cow milk hypersensitivity are frequent disorders of infancy. A possible causative association between these two entities has been suggested. Objective: The primary aim was to elucidate whether a causative relationship between the two entities could be established in a population of infants and children. A secondary aim was to evaluate whether cow milk challenge during esophageal pH monitoring is useful as an objective method to identify this subgroup of patients. Methods: Upper endoscopy followed by a 48-hour esophageal pH monitoring with cow’s milk elimination diet at day 1 and challenge at day 2. Cow milk hypersensitivity was later verified by elimination diet and a second open (in patients <3 years of age) or double-blind placebo-controlled (in patients ≥3 years of age) challenge. Skin prick test, specific serum immunoglobulin E and skin patch test were used as supplementary procedures. Follow-up endoscopy and pH monitoring were performed after 3 months of treatment (omeprazole versus elimination diet dependent on evidence of food hypersensitivity). Results: Eighteen of 42 investigated patients had severe GERD, defined as endoscopic esophagitis and/or a reflux index >10%. Among these patients, a group of 10 patients with GERD and cow milk hypersensitivity was identified. This group had a significantly higher reflux index compared with children with primary GERD. No significant increase was noted in reflux index during simultaneous pH monitoring and milk challenge. Conclusions: An association between GERD and cow milk hypersensitivity was observed in both infants and children with severe GERD. Simultaneous cow milk challenge and pH monitoring had limited value as a method to identify this subgroup.

Eosinophilic oesophagitis in infants and children in the region of southern Denmark: a prospective study of prevalence and clinical presentation.

Objective: Eosinophilic oesophagitis (EE) is a clinical entity characterised by a set of symptoms and eosinophilic infiltration of the oesophageal epithelium. Recent reports indicate that EE is increasingly diagnosed in paediatric patients. We aimed to evaluate the epidemiology of paediatric EE in a European population. Design: Infants and children in the Region of Southern Denmark were prospectively referred for further evaluation of symptoms of gastroesophageal reflux disease (GERD) after treatment failure with a proton pump inhibitor. The evaluation included endoscopy, 24-hour oesophageal pH-metry, histology of oesophageal biopsies, and investigations for food allergy (double-blind, placebo-controlled food challenge, skin prick test, S-IgE antibodies, atopy patch test). Results: Of the 78 referred patients, 28 qualified for a diagnosis of GERD. Six children had >15 eosinophils per high-power field in biopsies from the oesophageal mucosa and qualified for the diagnosis of EE. The median age at diagnosis was 9.6 years. In 4 of the 6 patients, food allergy was confirmed by double-blind, placebo-controlled food challenge. In the Region of Southern Denmark with a paediatric population of 256,164 between 0 and 16 years of age, a yearly incidence of EE of 0.16/10,000 was estimated. Conclusion: We report a European prospective study of EE. It was documented in 6 of 78 patients with symptoms of GERD corresponding to an annual incidence of 0.16/10,000 infants and children.

Gastroesophageal reflux disease and eosinophilic esophagitis in infants and children. A study of esophageal pH, multiple intraluminal impedance and endoscopic ultrasound.

Abstract Objective. Eosinophilic esophagitis (EE) and gastroesophageal reflux disease (GERD) in childhood share aspects of symptomatology. In order to characterize EE and GERD in infants and children with symptoms of GERD we performed a prospective investigation including prolonged esophageal pH measurement, multiple intraluminal impedance (MII) and esophageal wall estimation by endoscopic ultrasound (EUS). Material and methods. Infants and children (0–15 years) with typical symptoms of GERD persisting after a 14-days proton pump inhibitor trial were included in a prospective study protocol. Upper endoscopy and EUS of the esophageal wall were performed followed by combined esophageal MII and pH measurement for 24 h. Results. A total of 78 infants and children were investigated: EE patients (n = 6), GERD patients (n = 28) and a group of infants and children with normal investigations (n = 44). The GERD group did not show a significantly higher number of non-acid reflux episodes (p = 0.9) than the patients with normal investigations. In all patients gastroesophageal reflux regularly extended into the proximal esophagus. EUS in four EE patients suggested an increased thickness of the mucosal layers both in the distal and in the proximal part of the esophagus. Conclusions. Esophageal MII indicated that neutral non-acid reflux episodes do not occur frequently in pediatric GERD or in EE. MII and pH-metry indicated that the majority of reflux episodes both in patients and controls pass into the proximal esophagus. EUS measurements suggested in EE patients a thickened mucosa both in the proximal and the distal part of the esophagus as compared to children with GERD and disease controls.

Esophageal Atresia: Gastroesophageal functional follow-up in 5–15 year old children

PURPOSE Esophageal atresia (EA) is one of the most frequent congenital alimentary tract anomalies with a considerable morbidity throughout childhood. This study evaluates the gastroesophageal problems in 5-15 year old children with EA and aims to identify factors predisposing to esophagitis in EA. MATERIAL AND METHODS Fifty-nine patients primarily operated at Odense University Hospital, Denmark, during 1993-2005 were included in this follow-up study. The patients underwent the following examinations: Interview, upper endoscopy, endoscopic ultrasonography, high-resolution esophageal manometry (HREM), and pH- and multichannel intraluminal impedance (MII) measurements. Twenty-five patients with suspected gastro-esophageal reflux disease (GERD) underwent the same investigations and served as controls. RESULTS Median age was 10.2 years (7.1-13.3). Thirty-three (55.9%) presented with GERD symptoms, 41 (69.5%) with dysphagia, and 33 (55.9%) with respiratory symptoms. Twenty-nine (49.2%) had endoscopic esophagitis, and 26 (44.1%) histological esophagitis. Median reflux index (RI) was 8.3 (4.8-14.9). In 32 (55.2%) RI was above 7. Ten percent had eosinophilic inflammation. HREM showed dysmotility in the esophagus in all EA patients, 83.3% had no propagating swallows. No predictive factors predisposing the development of endoscopic esophagitis were identified. CONCLUSIONS Gastroesophageal problems in children born with EA are common. Routine follow-up with endoscopy and pH-metry in EA patients is warranted.

Eosinophilia in the upper gastrointestinal tract is not a characteristic feature in cow's milk sensitive gastro-oesophageal reflux disease. Measurement by two methodologies

Background: An association between cow’s milk hypersensitivity (CMH) and gastro–oesophageal reflux disease (GERD) in childhood has been reported in the past decade. Aim: To assess whether biopsies from the upper gastrointestinal tract of children with cow’s milk sensitive GERD have a specific allergic inflammatory pattern, and to compare two different techniques for measuring inflammatory cells in gastrointestinal biopsies. Methods: GERD was diagnosed by means of endoscopy and oesophageal pH monitoring. Hypersensitivity to cow’s milk was determined by an elimination diet and cow’s milk challenge. Allergic inflammatory cells in upper gastrointestinal biopsies were identified by immunohistochemistry and their numbers were assessed by two different methods—counting the number of cells/high power field and using the computerised Cast-Grid system. Results: Cow’s milk sensitive GERD was identified in 10 of 17 children with severe GERD (median age, 7.8 years). Biopsies from children with endoscopic oesophagitis had significantly increased numbers of mast cells and T cells. No differences in the number of eosinophils, mast cells, or T cells were found between children with CMH and those with primary GERD. Several differences were found between the two different histological quantification methods. Conclusions: CMH was found not only in infants but also in school age children with GERD. Histology did not identify the cow’s milk sensitive GERD subgroup. The computerised histological method provides a more complete evaluation based upon total biopsy area, and helped to limit the bias of uneven biopsy size.

Genetic polymorphisms of mannan binding lectin (MBL), serum levels of MBL, the MBL associated serine protease and H-ficolin in patients with Crohn’s disease

The observation of mannan binding lectin (MBL) expression in the small intestine1 suggests that MBL could be a component in the pathogenesis in Crohn’s disease. Seibold et al 2 recently compared the frequencies of MBL polymorphisms in 74 patients with Crohn’s disease with 32 healthy controls, and observed a significantly increased frequency of homozygous exon-1 variations. We evaluated the role of MBL polymorphisms, the MBL associated serine protease-2 (MASP-2) and H-ficolin in a cohort of Danish patients with Crohn’s disease. A total of 171 patients (73 males and 98 females) were evaluated. Age at onset of Crohn’s disease, localisation and disease behaviour were classified according to the Vienna classification.3 Plasma levels of MBL were measured by a functional time resolved immunofluorometric assay.4 Genetic variations in exon-1 …

Spinal cord injury at birth: a hidden causative factor

A case of perinatally acquired spinal cord injury (SCI) is presented. The foetus was vigorous until birth, the breech presented and delivery was performed by a non‐traumatic Caesarean section. The infant displayed symptoms of severe SCI but diagnosis was delayed due to severe co‐morbidity. Diagnostic considerations are briefly reviewed. Ventilatory support was withdrawn at the age of 20 days when the infant had still not exhibited any respiratory effort or spontaneous movements. Autopsy revealed a serious congenital malalignment of the upper cervical vertebrae and at the histological examination extensive reactive changes were observed in the same area. To our knowledge such findings have not been published previously.

Pediatric Inflammatory Bowel Diseases: Should We Be Looking for Kidney Abnormalities?

Background Kidney disease has been reported in adults with inflammatory bowel disease (IBD) and is regarded an extraintestinal manifestation or more rarely a side effect of the medical treatment. Methods In this cross-sectional study we describe the extent of kidney pathology in a cohort of 56 children with IBD. Blood and urine samples were analyzed for markers of kidney disease and ultrasonography was performed to evaluate pole-to-pole kidney length. Results We found that 25% of the patients had either previously reported kidney disease or ultrasonographic signs of chronic kidney disease. The median kidney size compared with normal children was significantly reduced. In a multivariate linear mixed model, small kidneys significantly correlated with the use of infliximab, whereas the use of enteral nutritional therapy was associated with larger kidneys. Conclusion Children with IBD are at risk of chronic kidney disease, and the risk seems to be increased with the severity of the disease.

Chronic diseases in the children of women with maternal thyroid dysfunction: a nationwide cohort study

Objective Maternal thyroid disease (TD) during pregnancy is associated with adverse birth outcomes, but little is known on its long-term outcomes. We aimed to examine if children born to mothers with TD have increased disease risk during childhood and adolescence. Patients and methods A register-based cohort study was conducted on all live born children in Denmark from 1989 to 2013, including the association between maternal TD during pregnancy and somatic and psychiatric diseases in the children. Cox proportional hazards models were used to compute hazard ratios (HRs) according to the type of maternal TD, Graves’ disease, and Hashimoto’s thyroiditis. Results A total of 2,618 children were born to women with Graves’ disease, 760 to women with Hashimoto’s thyroiditis (exposed), and 1,557,577 to women without any TD (unexposed). The median follow-up time for children born to mothers with Graves’ disease was 9.3 years (25/75 percentile 5.4/13.9 years) and with Hashimoto’s thyroiditis was 4.8 years (25/75 percentile 2.5/8.2 years). In children exposed to maternal Graves’ disease in utero, the adjusted HR of TD was 12.83 (95% CI, 9.74–16.90), Graves’ disease was 34.3 (95% CI, 20.23–58.35), and type 1 was diabetes 2.47 (95% CI, 1.46–4.18). In children exposed to maternal Hashimoto’s thyroiditis, the adjusted HR of Hashimoto’s thyroiditis was 24.04 (95% CI, 5.89–97.94). Conclusion Our data suggest that children born to women with Graves’ disease and Hashimoto’s thyroiditis have excess long-term morbidities in childhood and adolescence. We particularly found an increased risk of any TD and type 1 diabetes to be diagnosed in children exposed in utero to Graves’ disease. These novel findings are relevant for pediatricians, stressing the importance of history of maternal disease when evaluating children with suspected endocrine disorders.