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Background The aetiology of juvenile idiopathic arthritis (JIA) is poorly understood. It has been shown that use of antibiotics is associated with JIA. However, whether the association is due to increased occurrence of infection in these individuals is unknown. The purpose of this investigation was to measure the association between number of infections and use of antibiotics during childhood with development of JIA. Methods In ABIS (All Babies in Southeast Sweden) a population-based prospective birth cohort of 17,055 children, data were collected on infections and antibiotic exposure during pregnancy and childhood. 102 individuals with JIA were identified. Multivariable logistic regression analyses were performed, adjusting for confounding factors. Results Exposure to antibiotics during the periods 1–12 months, 1–3 years and 5–8 years was significantly associated with increased risk for JIA. The odds of developing JIA were three times higher in those exposed to antibiotics during the first 3 years of life compared with those not exposed (aOR 3.17; 95% CI 1.11–9.03, p = 0.031), and more than twice as high in those exposed to antibiotics during the first 5 years of life compared with those not exposed (aOR 2.18; 95% CI 1.36–3.50, p = 0.001). The odds of developing JIA were 78% higher in those exposed to antibiotics during the first 8 years of life compared with those not exposed (aOR 1.78; 95% CI 1.15–2.73, p = 0.009). Occurrence of infection during fetal life or childhood showed no significant association with the risk of developing JIA, after confounder adjustment. The cumulative number of courses of antibiotics was significantly higher during childhood for the individuals who developed JIA (p Conclusions Exposure to antibiotics early in life is associated with later onset of JIA in a large birth cohort from the general population. The relationship was dose dependent. These results suggest that further, more restrictive, antibiotic policies during the first years of life would be advisable.

Erik Kindgren,1,2 Antonia Quiñones Perez,1 Rajna Knez1,3 1Department of Pediatrics, Skaraborg Hospital, Skövde, Sweden; 2Division of Pediatrics, Department of Biomedical and Clinical Sciences (BKV), Medical Faculty, Linköping University, Linköping, Sweden; 3Sahlgrenska Academy, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, SwedenCorrespondence: Erik KindgrenDepartment of Pediatrics, Skaraborg Hospital, Lövängsvägen, Skövde, 541 42, SwedenTel +46104739222Fax +46500478356Email erik@kindgren.orgIntroduction: Hypermobility spectrum disorders (HSD) and hypermobile Ehlers-Danlos syndrome (hEDS) are both characterized by generalized hypermobility, in combination with pain, affected proprioception, and pronounced fatigue. Clinical observation indicates that behavioral problems, hyperactivity, and autistic traits are overrepresented in children with those conditions. The purpose of this retrospective study was to establish the prevalence of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) among children with HSD and hEDS treated in our clinic since 2012.Subjects and Methods: Since Ehlers-Danlos syndrome (EDS) diagnostic criteria and international classification were changed in 2017, we equate the older diagnosis EDS hypermobility type with the newer hEDS and the older hypermobility syndrome with HSD. A registry search from the computerized medical record system found 201 children (88 boys, 113 girls) aged 6– 18 years who were treated at our pediatrics department with the diagnoses HSD or EDS. All medical records (113 with HSD, 88 with EDS) were reviewed, and key symptoms such as fatigue and pain, as well as diagnosis of ADHD/ASD, were recorded.Results: All EDS cases could be classified as hEDS. Of the entire study cohort, 16% had a verified ADHD diagnosis and a further 7% were undergoing ADHD diagnostic investigation. Significantly more children with hEDS had ADHD compared to children with HSD (p=0.02). In the age group 15– 16 years, 35% of those with hEDS had ADHD and, among those aged 17– 18 years, ADHD was present in 46%. Children with coexisting ADHD showed a significantly higher proportion of associated symptoms such as fatigue, sleep-problems, and urinary tract problems. ASD had been verified in 6% of the children. Of those with ASD, 92% had sleep problems.Conclusion: This study shows a strong association between HSD or hEDS and ADHD or ASD. Therefore, children with HSD or hEDS may need to be routinely screened for neuropsychiatric symptoms.Keywords: ADHD, autism spectrum disorder, children, hypermobility spectrum disorder, Ehlers-Danlos syndrome

Background The aim of this study was to investigate relations between psychosocial factors, signs and symptoms of orofacial pain and jaw dysfunction in patients with juvenile idiopathic arthritis (JIA). Methods Forty-five patients with JIA (median age 12 years) and 16 healthy matched controls (median age 13 years) were examined according to the diagnostic criteria for temporomandibular disorders (DC/TMD). The subjects answered the DC/TMD questionnaires regarding psychosocial factors (pain intensity, pain–related disability, depression, stress, catastrophizing, pain locations and jaw function). Results JIA patients with orofacial pain had higher degree of stress, depression, catastrophizing and jaw dysfunction compared to subjects without. In turn, these factors were associated with orofacial pain intensity. Also, patients with orofacial pain had higher systemic inflammatory activity. Conclusions Orofacial pain in patients with JIA is associated with stress, psychological distress, jaw dysfunction and loss of daily living activities. Pain intensity seems to be the major pain aspect related to these factors. In addition, systemic inflammatory activity appears to be an important factor contributing to orofacial pain in JIA.

Background: Juvenile idiopathic arthritis (JIA) is considered to be an autoimmune disease, but the etiology is unknown. We decided to study the influence of early nutrition on later development of JIA. Methods: All parents with children born between October 1, 1997 and October 1, 1999 in Southeast Sweden were asked to participate in the ABIS prospective cohort study (All Babies in Southeast Sweden), At 1 year, questionnaires with information on breastfeeding and introduction of foods were completed by 10,565 families. We identified 32 children with JIA and 111 children with non-chronic arthritis with completed questionnaires after delivery and after 1 year. A multivariable logistic regression model, adjusted for relevant factors, was performed to calculate the association between JIA and feeding during the first year of life. Results: An increased risk for JIA was found in children who had breast fed for less than 4 months, as opposed to those who were continued on breast milk beyond 4 months of age (aOR 3.5, 95% CI 1.4-8,5; p = 0.006). A short duration of exclusive as well as total breastfeeding was associated with an increased risk of JIA (aOR 1.3, 95% CI 1.1-1.6; p = 0.008 and aOR 1.2, 95% CI 1.1-1.3; p amp;lt; 0.001). All associations between breastfeeding and JIA persisted after adjustment. There was no relationship between early nutrition and non-chronic arthritis. Conclusions: Our results indicate that there are different disease mechanisms for different types of arthritis in childhood. Longer duration of breastfeeding (both total and exclusive) may protect against development of JIA. Mothers should be encouraged to breast-feed their babies exclusively, if at all possible, for 4 months and continue partial breastfeeding for an extended time when foreign proteins are introduced. Funding Agencies|Research Unit of Kalmar County Council; Swedish Rheumatism Association; Jerring Foundation; Swedish Child Diabetes Foundation (Barndiabetesfonden); Juvenile Diabetes Research Foundation; Medical Research Council of Southeast Sweden (FORSS)

The sympathetic nervous system may be involved in the pathophysiology of insulin resistance and metabolic cardiovascular syndrome in young men. The aim was to study the effects of long-term stress on different features of the metabolic syndrome (MES) in formerly non-obese healthy young males during 5 months of defined conditions.Sixteen healthy male sailors (mean age 36.5 (SD)+/-7 years) participating in a sailing race around the world were recruited for the study. Investigations were done before the start and at stop overs after finishing laps 1, 2 and 4 (1, 2(1/2) and 5 months, respectively). Anthropometric and blood pressure data as well as biochemical data associated with MES were substantiated. Food intake and exercise were chartered and largely controlled. A mean weight loss of 4.5+/-2 kg (P0.005), comprising both fat and lean body mass, was recorded during the first lap. Subsequently after 5 months, a weight gain, mainly consisting of 1.2+/-1.1 kg body fat (P0.05), took place, concomitantly with a protein mass drop of 0.6+/-1.1 kg (P0.05). The body fat gain accumulated on the abdominal region. Elevated blood levels of HbA1c, insulin and the triglycerides/high-density lipoprotein ratio were also observed during the race. Likewise heart rate and systolic blood pressure increased slightly but to a statistically significant extent.Non-obese healthy young men exposed to long-term stress developed abdominal obesity and signs of a metabolic syndrome in embryo, also emphasized by biochemical and blood pressure alterations. It is suggested that long-term and sustained stress activation might be an additional risk factor for the development of MES, even after control of dietary and exercise habits.