PROBLEM: How maternal allergy affects the systemic and local immunological environment during pregnancy and the immune development of the offspring is unclear.

METHOD OF STUDY: Expression of 40 genes was quantified by PCR arrays in placenta, peripheral blood mononuclear cells (PBMC), and cord blood mononuclear cells (CBMC) from 7 allergic and 12 non-allergic women and their offspring.

RESULTS: Placental gene expression was dominated by a Th2-/anti-inflammatory profile, irrespectively of maternal allergy, as compared to gene expression in PBMC. p35 expression in placenta correlated with fetal Tbx21 (ρ = -0.88, P < 0.001) and IL-5 expression in PBMC with fetal galectin1 (ρ = 0.91, P < 0.001). Increased expression of Th2-associated CCL22 in CBMC preceded allergy development.

CONCLUSIONS: Gene expression locally and systemically during pregnancy was partly associated with the offspring's gene expression, possibly indicating that the immunological milieu is important for fetal immune development. Maternal allergy was not associated with an enhanced Th2 immunity in placenta or PBMC, while a marked prenatal Th2 skewing, shown as increased CCL22 mRNA expression, might contribute to postnatal allergy development.

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The complex and diverse intestinal microbiome is recognized as important in promoting human health. An altered gut microflora, referred to as dysbiosis, is increasingly recognized as having an etiologic role in a variety of conditions, including functional gastrointestinal disorders: colic in infants and irritable bowel syndrome in older children. Probiotics are defined as live microorganisms that, if ingested in sufficient amounts, restore microbial homeostasis and have a benefit on health. Randomized controlled trials indicate that probiotics can be effective in a variety of intestinal conditions, including colic and irritable bowel syndrome. Probiotics may promote gut microbial diversity, but timing of the intervention appears crucial. Strain-specific effects on colonization resistance, epithelial barrier integrity, modulation of signal transduction, impacts on innate and adaptive immune responses, and effects on visceral hyperalgesia likely explain the observed variability in various probiotic strains. In the future, probiotics are likely to be chosen for use in a defined clinical setting based on underlying mechanism(s) of action. The precise component of the probiotic agent mediating observed effects is the subject of current research. Unresolved issues relate to optimal dosages, timing of ingestion, single versus combination formulations, maintenance of viability in storage, and the merits of employing probiotic- derived products. (C) 2017 Nestec Ltd., Vevey/S. Karger AG, Basel

Limited microbial exposure is suggested to underlie the increase of allergic diseases in affluent countries, and bacterial diversity seems to be more important than specific bacteria taxa. Prospective studies indicate that the gut microbiota composition during the first months of life influences allergy development, and support the theory that factors influencing the early maturation of the immune system might be important for subsequent allergic disease. However, recent research indicates that microbial exposure during pregnancy may be even more important for the preventative effects against allergic disease. This review gives a background of the epidemiology, immunology, and microbiology literature in this field. It focuses on possible underlying mechanisms such as immune-regulated epigenetic imprinting and bacterial translocation during pregnancy, potentially providing the offspring with a pioneer microbiome. We suggest that a possible reason for the initial exposure of bacterial molecular patterns to the fetus in utero is to prime the immune system and/or the epithelium to respond appropriately to pathogens and commensals after birth.

Studying the extent to which children are exposed to victimizing events is important to fully understand the effect of such exposure in shaping them as adults. The aim of this study was to use self-report by adolescents to measure the prevalence of victimizing events and of poly-victimization. A representative sample of 5,960 students (aged 17) from high schools in Sweden was given the self-administrated version of the Juvenile Victimization Questionnaire (JVQ) along with questions concerning gender, birthplace, parents birthplace and employment, residence, educational program, and municipality size. The results show that 84.1% (83.0% young men and 85.2% young women) of the students had experienced victimization during their lifetime, and 10.3% were categorized as poly-victims (8.1% young men and 12.5% young women; OR = 1.62, 95% confidence interval [CI] = [1.35, 1.94]). Adolescents living with both parents were at lower risk of any form of victimization for both genders, while females were at higher risk of maltreatment, peer victimization, and, most significantly, sexual victimization. In conclusion, the vast majority of young people have been victimized during their lifetime. A greater awareness of the impact of these victimizing events on children and adolescents is important as a basis for providing a safer milieu and establishing better interventions, especially for those that have been victimized on multiple occasions. The high-exposure group was determined by using 10 events as a cutoff. Findings on this group corresponded with findings in other international studies regarding distribution, elevated risk for females, and the possibility of limiting the effects of victimization by modifying living conditions.

ObjectiveTo explore the relationship between certain clinical variables and metabolic HbA1c at diagnosis correlated to HbA1c at follow-up (p less than 0.001). There was a clear gender difference regarding HbA1c. Girls had higher values both at diagnosis and at follow-up (p less than 0.001). Girls also had lower BMI and pH at diagnosis than boys (p less than 0.001). In contrast, girls with the highest body mass index (BMI) at follow-up had higher mean HbA1c at follow-up in 2010 (p less than 0.001). Having a mother and/or a father with high BMI implied higher HbA1c at diagnosis (p less than 0.003). ConclusionsHbA1c at diagnosis seems to predict metabolic control years later. There is a gender difference at diagnosis as female patients have higher HbA1c than males at diagnosis as well as at follow up. As metabolic control is very much correlated to complications there is a need to early identify patients at risk of poor metabolic control. Even though we do not know whether a high HbA1c level is mainly due to severity of the disease or to behavioral patterns, new ways to treat and support these children, especially girls, are needed.

Aims: To evaluate how HbA1c in adolescents with type 1 diabetes affects microvascular complications in young adults. Methods: All individuals registered in the Swedish paediatric diabetes quality registry (SWEDIABKIDS) 13-18 years of age, and as adults registered in the Swedish National Diabetes Registry (NDR) in both the years 2011 and 2012 were included, in total 4250 individuals. Results: Of the individuals with mean HbA1c &gt;78 mmol/mol in SWEDIABKIDS 83.4% had retinopathy, 15.8% had microalbuminuria and 4.9% had macroalbuminuria in NDR. The logistic regression analysis showed that the OR to develop macroalbuminuria as a young adult was significantly higher in the group with mean HbA1c &gt;78 mmol/mol in SWEDIABKIDS (p &lt; 0.05). Among the patients with mean HbA1c above 78 mmol/mol in both registries there was a significantly higher proportion that had retinopathy, microalbuminuria (p &lt; 0.001) and/or macroalbuminuria (p &lt; 0.01) compared to the group with HbA1c below 57 mmol/mol in both registries. Only 6.5% of the persons in this study were over 30 years of age. Conclusions: Paediatric diabetes teams working with teenagers must be aware of the impact of good metabolic control during adolescence, and should intensify the care during this vulnerable period of life to reduce the risk of microvascular complications in young adults.

GAD is a major target of the autoimmune response that occurs in type 1 diabetes mellitus. Randomised controlled clinical trials of a GAD + alum vaccine in human participants have so far given conflicting results. In this study, we sought to see whether a clearer answer to the question of whether GAD65 has an effect on C-peptide could be reached by combining individual-level data from the randomised controlled trials using Bayesian meta-analysis to estimate the probability of a positive biological effect (a reduction in C-peptide loss compared with placebo approximately 1 year after the GAD vaccine). We estimate that there is a 98% probability that 20 mu g GAD with alum administered twice yields a positive biological effect. The effect is probably a 15-20% reduction in the loss of C-peptide at approximately 1 year after treatment. This translates to an annual expected loss of between -0.250 and -0.235 pmol/ml in treated patients compared with an expected 2 h AUC loss of -0.294 pmol/ml at 1 year for untreated newly diagnosed patients. The biological effect of this vaccination should be developed further in order to reach clinically desirable reductions in insulin loss in patients recently diagnosed with type 1 diabetes.

Treatment of type 1 diabetes has been intensified aiming at normalizing blood glucose, which may increase the risk of severe hypoglycemia (SH). We aimed to compare the incidence of SH events in the four Nordic countries Denmark, Iceland, Norway and Sweden, and to assess the influence of hemoglobin A1c (HbA1c) and treatment modalities on the frequency of SH; particularly, to explore if a HbA1c target =6.7% (50 mmol/mol) is feasible.

To date several studies have investigated the intergenerational effect of preterm and small-for-gestational-age births. However, most studies excluded both twin mothers and twin offspring from the analyses. Thus, the objective of this study was to investigate the intergenerational effect of preterm birth and small for gestational age (SGA) among twins and singletons.

A prospective population based register study of mother-first-born offspring pairs recorded in the Swedish Medical Birth Register was performed. The study included 4073 twins and 264,794 singletons born in 1973-1983 and their firstborns born in 1986-2009. Preterm birth was defined as birth <37 weeks of gestation and SGA as < 2 standard deviations of the Swedish standard. Logistic regressions were performed to estimate the intergenerational effect of each birth characteristic. Adjustments were made for maternal grandmothers and mother’s socio-demographic factors in addition to maternal birth- characteristics.

Among mothers born as singletons, being born preterm was associated with an increased risk for delivering a preterm child (adjusted OR 1.39, 95% CI 1.29-1.50) while being born SGA increased the likelihood of a SGA child (adjusted OR 3.04, 95% CI 2.80-3.30) as well as a preterm child (adjusted OR 1.30, 95% CI 1.20-1.40). In twin mothers, the corresponding ORs tended to be lower and the only statistically significant association was between a SGA mother and a SGA child (adjusted OR 2.15, 95% CI 1.40-3.31). A statistically significant interaction between twinning and mother’s size for gestational was identified in a multivariate linear regression analysis indicating that singleton mothers born SGA were associated with a lower birth weight compared to mothers not born SGA.

Preterm birth and SGA appear to be transferred from one generation to the next, although not always reaching statistical significance. These effects seem to be less evident in mothers born as twins compared with those born as singletons.

Background Twinning has been shown to be associated with a reduced reproductive rate compared to singletons. This can partly be explained by the birth-characteristics pertaining to twinning as many twins are born preterm, with low birth weight or small for gestational age. However, the intergenerational reproductive rate may also be due to familial factors such as number of siblings.

Methods This is a register-based study of all men and women born in Sweden between 1973 and 1993 who were living in Sweden at 13 years of age. Data on the study objects’ own births as well as their offspring, parental socio-demographic factors were collected from Swedish population based registers. Hazard ratios for the likelihood of becoming a parent were estimated using Cox’s proportion hazard models. All models were adjusted for socio-demographic and birth characteristics.

Results Adjusting for number of siblings, socio-demographic factors and birth characteristics, twinning was associated with a decreased likelihood of becoming a first-time parent, compared with singletons both for females (HR (95% CI)=0.90 (0.88-0.93) and males (HR (95% CI)=0.96 (0.93-0.99). Having 3 or more siblings increased the chance of becoming a first-time parent among both male twins (HR (95% CI)=1.17 (1.08-1.27)) and singletons (HR (95% CI)=1.16 (1.15-1.18)) compared to having fewer than 3 siblings. This increased likelihood of becoming a parent was also present among female twins (HR (95% CI)=1.18 (1.10-1.26)) and singletons (HR (95% CI)=1.22 (1.21-1.24)).

Conclusions Twins have a decreased likelihood of becoming a parent compared to singletons even when adjusting for number of siblings.

Background

Individuals with body dysmorphic disorder (BDD) are highly distressed due to defects they perceive in their physical appearance that are not noticeable to others. The condition often leads to impaired functioning in relationships, socialization, and intimacy and a decreased ability to function in work, school, or other daily activities. Although BDD seems to be relatively prevalent, it is under-recognized by people in general and by health care professionals. Individuals with BDD are secretive about their symptoms, and they usually do not recognize that they are suffering from a psychiatric disorder. Instead, in an attempt to relieve their symptoms by correcting their perceived defects, they commonly seek dermatological treatment or cosmetic surgery. However, such interventions usually do not result in any decrease in BDD symptom severity, but can rather aggravate the symptoms. Therefore, it is crucial that health care professionals recognize BDD in order to offer adequate care. Prior to the studies conducted for this thesis, there were no known data regarding the prevalence of BDD in Sweden.

Main aims

(i) To translate a screening questionnaire for BDD (the Body Dysmorphic Disorder Questionnaire, BDDQ) into Swedish and validate the questionnaire in a community sample. (ii) To estimate the prevalence of BDD in the general population of Swedish women and in female dermatology patients. (iii) To explore BDD patients’ experiences of living with the disorder, including their experiences of the health care system.

Methods

The BDDQ was validated using the Structured Clinical Interview for DSM-IV (SCID) as the gold standard for diagnosing BDD (Study I). The validated BDDQ was used to estimate the prevalence of BDD in a randomly selected population-based sample of Swedish women (n=2 885) (Study II) and in a consecutive sample of female dermatology patients (n=425) (Study III). In Studies II and III, the Hospital Anxiety and Depression Scale was used to assess symptoms of depression and anxiety. In Study III, quality of life was evaluated by the Dermatology Life Quality Index. BDD patients’ lived experiences were explored using a qualitative research design (Study IV). Fifteen individuals with BDD were interviewed, and the interviews were analysed using Interpretive Description.

Results

The Swedish translation of the BDDQ displayed a sensitivity of 94%, a specidicity of 90% and a (positive) likelihood ratio of 9.4. The prevalence of women screening positive for BDD was 2.1% (95% CI 1.7–2.7) in the population-based sample of women and 4.9% (95% CI 3.2–7.4) in the dermatology patients’ sample. The positive predictive value of the BDDQ (71%) gave an estimated BDD prevalence of 1.5% (95% CI 1.1–2.0) in the female Swedish population. Women screening positive for BDD had signidicantly more symptoms of anxiety and depression compared to those screening negative for BDD in both samples. In the dermatology patients, quality of life was severely impaired in patients with positive BDD screening. The overarching concept found in Study IV was that patients with BDD felt imprisoned and were struggling to become free and to no longer feel abnormal. The participants had encountered difdiculties in accessing health care and had disappointing experiences of the health care system.

Conclusion

The findings of this thesis indicate that BDD is a relatively common disorder in the Swedish female population, and that it is more prevalent in dermatology patients. BDD patients struggle to be free from a feeling of imprisonment, and in this struggle they encounter difficulties in accessing health care. Therefore, it is important to increase awareness and recognition of BDD among health care professionals to ensure that patients with BDD receive the appropriate care.

Objectives: The purpose of this study was to explore the experiences of patients living with body dysmorphic disorder (BDD), including their experiences with the health care system. Methods: Fifteen individuals with BDD were interviewed, and interpretive description was used to analyse the interviews. Results: The following six themes were identified: being absorbed in time-consuming procedures, facing tension between ones own ideal and the perceived reality, becoming the disorder, being restricted in life, attempting to reduce ones problems and striving to receive care. The overarching concept derived from the themes was feeling imprisoned - struggling to become free and to no longer feel abnormal. Conclusions: Ideas of imprisonment and abnormality compose the entire experience of living with this disorder. Although the participants suffered greatly from their BDD, these patients encountered difficulties in accessing health care and had disappointing experiences during their encounters with the health care system. Therefore, it is important to increase awareness and knowledge of BDD among health care professionals to ensure that patients with BDD receive the appropriate care.

Background: Body dysmorphic disorder (BDD) is characterized by a highly distressing and impairing preoccupation with nonexistent or slight defects in appearance. Patients with BDD present to both psychiatric and non-psychiatric physicians. A few studies have assessed BDD prevalence in representative samples of the general population and have demonstrated that this disorder is relatively common. Our primary objective was to assess the prevalence of BDD in the Swedish population because no data are currently available. Methods: In the current cross-sectional study, 2891 randomly selected Swedish women aged 18-60 years participated. The occurrence of BDD was assessed using the Body Dysmorphic Disorder Questionnaire (BDDQ), which is a validated self-report measure derived from the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV criteria for BDD. In addition, symptoms of depression and anxiety were measured using the Hospital Anxiety and Depression Scale (HADS). Results: The prevalence of BDD among Swedish women was 2.1%. The women with BDD had significantly more symptoms of depression and anxiety than the women without BDD. Depression (HADS depression score greater than= 8) and anxiety (HADS anxiety score greater than= 8) were reported by 42% and 72% of the women with BDD, respectively. Conclusions: The results of the present study indicate that BDD is relatively common among Swedish women (2.1%) and that it is associated with significant morbidity.

BackgroundIndividuals with body dysmorphic disorder (BDD) are highly distressed and impaired owing to perceived defects in their physical appearance that are not noticeable to others. They are frequently concerned about their skin and often present to dermatologists rather than psychiatrists. However, BDD patients attending dermatology clinics may be at risk of not receiving an appropriate assessment and beneficial treatment. The aims of this study were to estimate the BDD prevalence rate among Swedish female dermatology patients and to assess the psychological condition of BDD patients compared to that of other dermatology patients. MethodsThe occurrence of BDD was estimated using the Body Dysmorphic Disorder Questionnaire (BDDQ), a validated self-report measure for BDD. Symptoms of depression and anxiety were measured by the Hospital Anxiety and Depression Scale (HADS), and quality of life was assessed using the Dermatology Life Quality Index (DLQI). ResultsThe prevalence rate of BDD among female Swedish dermatology patients was 4.9% (95% CI 3.2-7.4). Anxiety (HADS A11) was 4-fold more commonly reported by patients with positive BDD screening (48% vs. 11%), and depression (HADS D11) was over 10-fold more common in patients with positive BDD screening (19% vs. 1.8%) (Pamp;lt;0.001). The median DLQI score was 18 in the BDD group, compared to a score of 4 in the non-BDD group (Pamp;lt;0.001). ConclusionsOur results indicate that BDD is fairly common among female Swedish dermatology patients (4.9%) and that BDD patients have high levels of depression and anxiety and severely impaired quality of life.

Physical activity in children is associated with several positive health outcomes such as decreased cardiovascular risk factors, improved lung function, enhanced motor skill development, healthier body composition, and also improved defense against inflammatory diseases. We examined how high physical activity vs a sedentary lifestyle in young children influences the immune response with focus on autoimmunity. Peripheral blood mononuclear cells, collected from 55 5-year-old children with either high physical activity (n = 14), average physical activity (n = 27), or low physical activity (n = 14), from the All Babies In Southeast Sweden (ABIS) cohort, were stimulated with antigens (tetanus toxoid and beta-lactoglobulin) and autoantigens (GAD65 , insulin, HSP60, and IA-2). Immune markers (cytokines and chemokines), C-peptide and proinsulin were analyzed. Children with high physical activity showed decreased immune activity toward the autoantigens GAD65 (IL-5, P < 0.05), HSP60 and IA-2 (IL-10, P < 0.05) and also low spontaneous pro-inflammatory immune activity (IL-6, IL-13, IFN-γ, TNF-α, and CCL2 (P < 0.05)) compared with children with an average or low physical activity. High physical activity in young children seems to have positive effects on the immune system by altering autoantigen-induced immune activity.

Background: Although immune responses directed against antigens from the intestinal microbiota are observed in certain diseases, the normal human adaptive immune response to intestinal microbiota is poorly defined. Objective: Our goal was to assess the adaptive immune response to the intestinal microbiota present in 143 healthy adults and compare this response with the response observed in 52 children and their mothers at risk of having allergic disease. Methods: Human serum was collected from adults and children followed from birth to 7 years of age, and the serum IgG response to a panel of intestinal microbiota antigens was assessed by using a novel protein microarray. Results: Nearly every subject tested, regardless of health status, had serum IgG that recognized a common set of antigens. Seroreactivity to the panel of antigens was significantly lower in atopic adults. Healthy infants expressed the highest level of IgG seroreactivity to intestinal microbiota antigens. This adaptive response developed between 6 and 12 months of age and peaked around 2 years of age. Low IgG responses to certain clusters of microbiota antigens during infancy were associated with allergy development during childhood. Conclusions: There is an observed perturbation of the adaptive response to antigens from the microbiota in allergic subjects. These perturbations are observable even in childhood, suggesting that optimal stimulation of the adaptive immune system by the microbiota might be needed to prevent certain immune-mediated diseases.

CONTEXT: Studies on clinical and immunological features of Autoimmune Addison's disease (AAD) are needed to understand the disease burden and increased mortality.

OBJECTIVE: To provide upgraded data on autoimmune comorbidities, replacement therapy, autoantibody profiles and cardiovascular risk factors.

DESIGN, SETTING AND PARTICIPANTS: Cross sectional, population-based study. 660 AAD patients were included utilizing the Swedish Addison Registry (SAR) 2008-2014. When analyzing cardiovascular risk factors, 3,594 individuals from the population-based survey in Northern Sweden, MONICA (MONItoring of Trends and Determinants of CArdiovascular Disease), served as controls.

MAIN OUTCOME MEASURE: Prevalence of autoimmune comorbidities and cardiovascular risk factors. Autoantibodies against 13 autoantigens were determined.

RESULTS: Sixty percent of the SAR cohort consisted of females. Mean age at diagnosis was significantly higher for females than for males (36.8 vs. 31.1 years). The proportion of 21-hydroxylase autoantibody positive patients was 83% and 62% of patients had one or more associated autoimmune diseases, more frequently coexisting in females (p<0.0001). AAD patients had lower BMI (p<0.0001) and prevalence of hypertension (p=0.027) compared with controls. Conventional hydrocortisone tablets were used by 89% of patients; with the mean dose 28.1±8.5 mg/day. The mean hydrocortisone equivalent dose normalized to body surface was 14.8±4.4 mg/m(2)/day. Higher hydrocortisone equivalent dose was associated with higher incidence of hypertension (p=0.046).

CONCLUSIONS: Careful monitoring of AAD patients is warranted to detect associated autoimmune diseases. Contemporary Swedish AAD patients do not have increased prevalence of overweight, hypertension, T2DM or hyperlipidemia. However, high glucocorticoid replacement doses may be a risk factor for hypertension.

Aim: Children treated with a growth hormone (GH) for idiopathic growth hormone deficiency (IGHD) may be monitored with the first-year prediction model from the Pfizer International Growth Database (KIGS) using auxology, age, GH dose and the maximum GH concentration from a stimulation test (GH(max)stim). We tested the hypothesis that using a 12-hour spontaneous profile (GH(max)12h) would be as accurate. Methods: We studied 98 prepubertal Swedish children (78boys) aged2-12 years enrolled in KIGS. The first-year growth was predicted using the GH(max) from the GHprofile and a stimulation test, and both of these were compared separately with the observed growth response. Results: The increased height observed in the first year was 0.74 standard deviation scores (SDS), and the studentised residuals for the predicted and observed growth with GH(max)stim (-0.16 SDS) and GH(max)12h (-0.22) were similar. Individual predictions calculated with stimulated or spontaneous GH(max) showed a significant correlation (r = 0.80). Conclusion: We validated the KIGS IGHD prediction model and found that the stimulated GH(max) peak can be reliably replaced by the GH(max) 12h with similar accuracy. This makes the model more accessible for clinicians, who can then provide realistic expectations for the growth response during the first year of treatment.

Background: Although a reduced gut microbiota diversity and low mucosal total IgA levels in infancy have been associated with allergy development, IgA responses to the gut microbiota have not yet been studied. Objective: We sought to determine the proportions of IgA coating together with the characterization of the dominant bacteria, bound to IgA or not, in infant stool samples in relation to allergy development. Methods: A combination of flow cytometric cell sorting and deep sequencing of the 16S rDNA gene was used to characterize the bacterial recognition patterns by IgA in stool samples collected at 1 and 12 months of age from children staying healthy or having allergic symptoms up to 7 years of age. Results: The children with allergic manifestations, particularly asthma, during childhood had a lower proportion of IgA bound to fecal bacteria at 12months of age compared with healthy children. These alterations cannot be attributed to differences in IgA levels or bacterial load between the 2 groups. Moreover, the bacterial targets of early IgA responses (including coating of the Bacteroides genus), as well as IgA recognition patterns, differed between healthy children and children with allergic manifestations. Altered IgA recognition patterns in children with allergy were observed already at 1 month of age, when the IgA antibodies are predominantly maternally derived in breast-fed children. Conclusion: An aberrant IgAresponsiveness to the gutmicrobiota during infancy precedes asthma and allergy development, possibly indicating an impaired mucosal barrier function in allergic children.

AIMS AND OBJECTIVES:

To explore and describe how parents of preterm and/or sick infants in neonatal care perceive their sleep.

BACKGROUND:

Parents experience many stressful situations when their newborn infant is preterm and/or sick. This affects bonding. By developing more family-centred care units with single-family rooms, parents are given the opportunity to stay and care for their newborn infant(s) 24 hours a day. Lack of sleep may affect new parents' ability to cope with the many challenges they face on a daily basis.

DESIGN:

A phenomenographic study with an inductive and exploratory design.

METHODS:

Semi-structured interviews were conducted with twelve parents of infants in neonatal care between January-March 2012. To describe variations in perception of the phenomenon, data were analysed using phenomenography.

FINDINGS:

Four descriptive categories were identified within the phenomenon sleep in parents of preterm and/or sick infants in neonatal care: impact of stress on sleep; how the environment affects sleep; keeping the family together improves sleep; and, how parents manage and prevent tiredness.

CONCLUSION:

Anxiety, uncertainty and powerlessness have a negative influence on sleep. This can be decreased by continuous information, guidance and practical support. Skin-to-skin care was perceived as a stress-reducing factor that improved relaxation and sleep and should be encouraged by the nurse. The parents also mentioned the importance of being together. Having a private place where they could relax and take care of themselves and their newborn infant improved sleep. It was also desirable to involve older siblings in order to decrease feelings of loneliness, sadness and isolation.

RELEVANCE FOR CLINICAL PRACTICE:

Improved parental sleep in neonatal care may help the families cope with the situation and facilitate problem-solving, emotional regulation and the transition to parenthood.

Background

Parents experience many stressful situations when their newborn infant is preterm and/or sick. This affects bonding. By developing more family-centered care units with single-family rooms, parents are given the opportunity to stay and care for their newborn infant(s) twenty-four hours a day. Lack of sleep may affect the new parents’ ability to handle the situation.

Aim

To explore and describe how parents of preterm and/or sick infants in neonatal care perceive their sleep.

Methods This is a phenomenographic study with an inductive, exploratory design. Semi-structured interviews were conducted with twelve parents of infants in neonatal care. Data was analysed to describe variations of the phenomenon.

Findings

Four descriptive categories were identified within the phenomenon sleep in parents of preterm and/or sick infants in neonatal care; Impact of stress on sleep, How the environment affects sleep, Keeping the family together improves sleep, and How parents manage and prevent tiredness.

Conclusion

Anxiety, uncertainty and powerlessness have a negative influence on sleep. This can be decreased by continuous information, guidance, and practical support. Skin-to-skin-care is an important source for recovery, relaxation and sleep, and should be encouraged by the nurse. The parents also mentioned the importance of being together. To have a private place where they could relax and take care of themselves and their newborn infant improved sleep. It was also desirable to involve older siblings in order to decrease feelings of loneliness, sadness and isolation. Improved parental sleep in the neonatal care may help the families to cope with the situation, and facilitate problem-solving, emotional regulation, and the transition to parenthood.

Introduction: The conventional ECG is commonly used to screen for hypertrophic cardiomyopathy (HCM), but up to 25% of adults and possibly larger percentages of children with HCM have no distinctive abnormalities on the conventional ECG, whereas 5 to 15% of healthy young athletes do. Recently, a 5-min resting advanced 12-lead ECG test ("A-ECG score") showed superiority to pooled criteria from the strictly conventional ECG in correctly identifying adult HCM. The purpose of this study was to evaluate whether in children and young adults, A-ECG scoring could detect echocardiographic HCM associated with the MYBPC3 genetic mutation with greater sensitivity than conventional ECG criteria and distinguish healthy young controls and athletes from persons with MYBPC3 HCM with greater specificity. Methods: Five-minute 12-lead ECGs were obtained from 15 young patients (mean age 13.2 years, range 0-30 years) with MYBPC3 mutation and phenotypic HCM. The conventional and A-ECG results of these patients were compared to those of 198 healthy children and young adults (mean age 13.2, range 1 month-30 years) with unremarkable echocardiograms, and to those of 36 young endurance-trained athletes, 20 of whom had athletic (physiologic) left ventricular hypertrophy. Results: Compared with commonly used, age-specific pooled criteria from the conventional ECG, a retrospectively generated A-ECG score incorporating results from just 2 derived vectorcardiographic parameters (spatial QRS-T angle and the change in the vectorcardiographic QRS azimuth angle from the second to the third eighth of the QRS interval) increased the sensitivity of ECG for identifying MYBPC3 HCM from 46% to 87% (p amp;lt; 0.05). Use of the same score also demonstrated superior specificity in a set of 198 healthy controls (94% vs. 87% for conventional ECG criteria; p amp;lt; 0.01) including in a subset of 36 healthy, young endurance-trained athletes (100% vs. 69% for conventional ECG criteria, p amp;lt; 0.001). Conclusions: In children and young adults, a 2-parameter 12-lead A-ECG score is retrospectively significantly more sensitive and specific than pooled, age-specific conventional ECG criteria for detecting MYBPC3-HCM and in distinguishing such patients from healthy controls, including endurance-trained athletes. (C) 2016 Elsevier Inc. All rights reserved.

Hypertrophic cardiomyopathy (HCM) is a major cause of sudden cardiac death in the young. Based on previous reports of functional abnormalities in not only coronary but also peripheral vessels in adults with HCM, we aimed to assess both peripheral vascular and myocardial diastolic function in young individuals with an early stage of HCM and in individuals at risk for HCM. Children, adolescents, and young adults (mean age: 12 yr) with a family history of HCM who either had (HCM group; n = 36) or did not have (HCM-risk group; n = 30) echocardiography-documented left ventricular (LV) hypertrophy as well as healthy matched controls (n = 85) and healthy young athletes (n = 12) were included in the study. All underwent assessment with 12-lead electrocardiography, two-dimensional echocardiography, tissue Doppler imaging and laser Doppler with transdermal iontophoresis of ACh and sodium nitroprusside. LV thickness and mass were increased in HCM and athlete groups compared with control and HCM-risk groups. The mitral E-to-e ratio, measured via tissue Doppler, was increased in HCM (P less than 0.0001) and HCM-risk (P less than 0.01) groups compared with control and athlete groups, as were microvascular responses to ACh (HCM group: P less than 0.045 and HCM- risk group: P less than 0.02). Responses to ACh correlated with the E-to-e ratio (r = 0.5, P = 0.001). Microvascular responses to sodium nitroprusside were similar in all groups (P = 0.2). HCM-causing mutations or its familial history are associated with changes in cardiac diastolic function and peripheral microvascular function even before the onset of myocardial hypertrophy. Tissue Doppler can be used to differentiate HCM from physiological LV hypertrophy in young athletes.

Objective: To examine the relationship between diabetes distress and gender, and the association with glycemic control, social support, health behaviors, and socio-economic status. Methods: All adolescents, aged 15 to 18 years, in the national, pediatric diabetes registry SWE-DIABKIDS with type 1 diabetes were invited to complete an online questionnaire. A total of 2112 teenagers were identified. Results: 453 complete responses were valid for analyses. Young women scored significantly higher on the distress-screening instrument DDS-2. Almost half of the female respondents exhibited moderate to severe diabetes distress-more than twice the proportion than among male respondents (44% vs 19%). Females reported twice as high scores on the fear of hypoglycemia scale (P amp;lt; 0.0001) and had a higher HbA1c value than males (P amp;lt; 0.0001). Gender was highly correlated with distress level even when controlling for multiple factors that may affect distress (parameter(female) = 0.4, P = 0.0003). Particular social problems were highly significant, that is, those who trust that their parents can handle their diabetes when necessary were significantly less distressed than others (P = 0.018). Higher HbA1c levels were associated with higher distress scores (P = 0.0005 [female], P = 0.0487 [male]). Conclusions: Diabetes-related distress is a great burden for adolescents living with diabetes. Actively involved family and friends may reduce diabetes distress, but female adolescents appear to be particularly vulnerable and may need extra focus and support. Our findings indicate that pediatric diabetes teams working with teenagers must intensify the care during this vulnerable period of life in order to reduce the risk of both psychological and vascular complications in young adults.

Expectations prior to needle-related procedures can influence individuals decision making and compliance with immunization programmes. To protect from human papilloma virus (HPV) and cervical cancer, the immunization needs to be given before sexual debut raising interest for this studys aim to investigate how 11 to 12-year-old girls narrate about their expectations prior to HPV vaccination. A total of 27 girls aged 11 to 12 years participated in this qualitative narrative study by writing short narratives describing their expectations. The requirement for inclusion was to have accepted HPV vaccination. Data were subjected to qualitative content analysis. Findings showed the following expectations: going to hurt, going to be scared and going to turn out fine. The expectations were based on the girls previous experiences, knowledge and self-image. The latent content revealed that the girls tried to transform uneasiness to confidence. The conclusion drawn from this study is that most girls of this age seem confident about their ability to cope with possible unpleasantness related to vaccinations. However, nurses need to find strategies to help those children who feel uneasy about needle-related procedures.

(1) Background: Assessing the quality of growth in premature infants is important in order to be able to provide them with optimal nutrition. The Pea Pod device, based on air displacement plethysmography, is able to assess body composition of infants. However, this method has not been sufficiently evaluated in premature infants; (2) Methods: In 14 infants in an age range of 3-7 days, born after 32-35 completed weeks of gestation, body weight, body volume, fat-free mass density (predicted by the Pea Pod software), and total body water (isotope dilution) were assessed. Reference estimates of fat-free mass density and body composition were obtained using a three-component model; (3) Results: Fat-free mass density values, predicted using Pea Pod, were biased but not significantly (p &gt; 0.05) different from reference estimates. Body fat (%), assessed using Pea Pod, was not significantly different from reference estimates. The biological variability of fat-free mass density was 0.55% of the average value (1.0627 g/mL); (4) Conclusion: The results indicate that the Pea Pod system is accurate for groups of newborn, moderately premature infants. However, more studies where this system is used for premature infants are needed, and we provide suggestions regarding how to develop this area.

Respiratory tract infections (RTI) are common among young children, and congenital heart defect (CHD) is a risk factor for severe illness and hospitalization. This study aims to assess the relative risk of hospitalization due to RTI in winter and summer seasons for different types of CHD. All children born in Sweden and under the age of two, in 2006-2011, were included. Heart defects were grouped according to type. Hospitalization rates for respiratory syncytial virus (RSV) infection and RTI in general were retrieved from the national inpatient registry. The relative risk of hospitalization was calculated by comparing each subgroup to other types of CHD and otherwise healthy children. The relative risk of hospitalization was increased for all CHD subgroups, and there was a greater increase in risk in summer for the most severe CHD. This included RSV infection, as well as RTI in general. The risk of hospitalization due to RTI is greater for CHD children. Prophylactic treatment with palivizumab, given to prevent severe RSV illness, is only recommended during winter. We argue that information to healthcare staff and parents should include how the risk of severe infectious respiratory tract illnesses, RSV and others, is present all year round for children with CHD.

BACKGROUND:

Sweden has the second highest incidence of type 1 diabetes in the world. Nutritional aspects in utero and in infancy affect the development. We conducted a survey to determine whether reported maternal use of vitamin D-containing micronutrient supplements during pregnancy was associated with the risk of developing type 1 diabetes in the child.

METHODS:

This report was based on data from the ABIS (All Babies In Southeast Sweden) study, with questionnaire data on 16 339 mother and infant pairs at birth and at 1-yr of age (n = 10 879), of whom 108 children were registered with type 1 diabetes before 14-16 yr of age. The questions 'during pregnancy, did you take any vitamin/mineral supplements?' and 'if yes, which? (open answer)' in addition to other lifestyle questions were answered. Logistic regression was performed with onset of type 1 diabetes as the dependent variable and vitamin D supplementation use as the independent variable, adjusted for relevant factors.

RESULTS:

Vitamin D supplementation during pregnancy was consumed by 9.3% of mothers whose children later got type1 diabetes and among 11.3% of those mothers whose children did not get type 1 diabetes (p = 0.532). No significant association was found between reported supplement intake of vitamin D during pregnancy and risk of type 1 diabetes, even when adjusting for factors which could influence the association.

CONCLUSION:

Maternal use of vitamin D-containing multivitamin supplements during pregnancy was not related to the risk of developing type 1 diabetes in children before 14-16 yr of age in Southeast of Sweden.

Aim To further elucidate the relationship between physical activity and several risk factors for development of diabetes (glucose, C-peptide and obesity) over time. Methods A prospective longitudinal study where physical activity was measured on 199 children from Kalmar and Linkoping at age 8, and the same 107 children from Linkoping again at age 12. Anthropometric data was collected and blood was analyzed for C-peptide and f-glucose. The children in the study were representative for the general Swedish child population, and on an average lean. Results High physical activity was related to lower C-peptide at age 8 and 12. This correlation was especially pronounced in boys, who also were more physically active than girls at both time points. The association seen at 8 years of age was similar at age 12 in most children. Children with higher BMI Z-Score had a higher fasting C-peptide (age 12) but linear regression showed that children with more steps per day were less likely to have a higher fasting C-peptide irrespective of BMI. Longitudinal follow-up showed that a decrease in physical activity increased insulin resistance and beta-cell load. Conclusions Already in young children, physical activity improves insulin sensitivity and decreases the need of C-peptide over time. This seems to become even more pronounced with increasing age when children are followed longitudinally. Low physical activity increases the load on insulin producing beta-cells, might increase the risk for both type 1- and 2 diabetes.

BACKGROUND:

Cortisol concentrations in plasma display a circadian rhythm in adults and children older than one year. Earlier studies report divergent results regarding when cortisol circadian rhythm is established. The present study aims to investigate at what age infants develop a circadian rhythm, as well as the possible influences of behavioral regularity and daily life trauma on when the rhythm is established. Furthermore, we determine age-related reference intervals for cortisol concentrations in saliva during the first year of life.

METHODS:

130 healthy full-term infants were included in a prospective, longitudinal study with saliva sampling on two consecutive days, in the morning (07:30-09:30), noon (10:00-12:00) and evening (19:30-21:30), each month from birth until the infant was twelve months old. Information about development of behavioral regularity and potential exposure to trauma was obtained from the parents through the Baby Behavior Questionnaire and the Life Incidence of Traumatic Events checklist.

RESULTS:

A significant group-level circadian rhythm of salivary cortisol secretion was established at one month, and remained throughout the first year of life, although there was considerable individual variability. No correlation was found between development of cortisol circadian rhythm and the results from either the Baby Behavior Questionnaire or the Life Incidence of Traumatic Events checklist. The study presents salivary cortisol reference intervals for infants during the first twelve months of life.

CONCLUSIONS:

Cortisol circadian rhythm in infants is already established by one month of age, earlier than previous studies have shown. The current study also provides first year age-related reference intervals for salivary cortisol levels in healthy, full-term infants.

Background Cortisol concentrations in plasma display a circadian rhythm in adults and children older than one year. Earlier studies report divergent results regarding when cortisol circadian rhythm is established. The present study aims to investigate at what age infants develop a circadian rhythm, as well as the possible influences of behavioral regularity and daily life trauma on when the rhythm is established. Furthermore, we determine age-related reference intervals for cortisol concentrations in saliva during the first year of life. Methods 130 healthy full-term infants were included in a prospective, longitudinal study with saliva sampling on two consecutive days, in the morning (07:30-09:30), noon (10:00-12:00) and evening (19:30-21:30), each month from birth until the infant was twelve months old. Information about development of behavioral regularity and potential exposure to trauma was obtained from the parents through the Baby Behavior Questionnaire and the Life Incidence of Traumatic Events checklist. Results A significant group-level circadian rhythm of salivary cortisol secretion was established at one month, and remained throughout the first year of life, although there was considerable individual variability. No correlation was found between development of cortisol circadian rhythm and the results from either the Baby Behavior Questionnaire or the Life Incidence of Traumatic Events checklist. The study presents salivary cortisol reference intervals for infants during the first twelve months of life. Conclusions Cortisol circadian rhythm in infants is already established by one month of age, earlier than previous studies have shown. The current study also provides first year age-related reference intervals for salivary cortisol levels in healthy, full-term infants.

OBJECTIVES: To investigate at what age preterm infants develop a salivary cortisol circadian rhythm and identify whether it is dependent on gestational age and/or postnatal age. To evaluate whether salivary cortisol circadian rhythm development is related to behavioral regularity. To elucidate salivary cortisol levels in preterm infants during the first year of life.

METHODS: This prospective, longitudinal study included 51 preterm infants. 130 healthy full-term infants served as controls. Monthly salivary cortisol levels were obtained in the morning (07:30-09:30), at noon (10:00-12:00), and in the evening (19:30-21:30), beginning at gestational age week 28-32 and continuing until twelve months corrected age. Behavioral regularity was studied using the Baby Behavior Questionnaire.

RESULTS: A salivary cortisol circadian rhythm was established by one month corrected age and persisted throughout the first year. The preterm infants showed a cortisol pattern increasingly more alike the full-term infants as the first year progressed. The preterm infants increase in behavioral regularity with age but no correlation was found between the development of salivary cortisol circadian rhythm and the development of behavior regularity. The time to establish salivary cortisol circadian rhythm differed between preterm and full-term infants according to postnatal age (p = 0.001) and was dependent on gestational age. Monthly salivary cortisol levels for preterm infants from birth until twelve months are presented. Additional findings were that topical corticosteroid medication was associated with higher concentrations of salivary cortisol (p = 0.02) and establishment of salivary cortisol circadian rhythm occurred later in infants treated with topical corticosteroid medication (p = 0.02).

CONCLUSIONS: Salivary cortisol circadian rhythm is established by one month corrected age in preterm infants. Establishment of salivary cortisol circadian rhythm is related to gestational age rather than to postnatal age. Salivary cortisol circadian rhythm development is not related to behavioral regularity.

Aim To explore prospectively the correlation between the level of pedometer-determined physical activity at the start of the study and the change in pulse wave velocity from baseline to 4 years later in people with Type 2 diabetes.

Methods We analysed data from 135 men and 53 women with Type 2 diabetes, aged 54–66 years. Physical activity was measured with waist-mounted pedometers on 3 consecutive days and the numbers of steps/day at baseline were classified into four groups: <5000 steps/day, 5000–7499 steps/day, 7500–9999 steps/day and ≥10 000 steps/day. Pulse wave velocity was measured using applanation tonometry over the carotid and femoral arteries at baseline and after 4 years.

Results The mean (±sd; range) number of steps/day was 8022 (±3765; 956–20 921). The participants with the lowest level of physical activity had a more pronounced increase in the change in pulse wave velocity compared with the participants with the highest. When change in pulse wave velocity was analysed as a continuous variable and adjusted for sex, age, diabetes duration, HbA1c, BMI, systolic blood pressure, pulse wave velocity at baseline, β-blocker use, statin use, unemployment, smoking and diabetes medication, the number of steps/day at baseline was significantly associated with a less steep increase in change in pulse wave velocity (P=0.005). Every 1000 extra steps at baseline corresponded to a lower increase in change in pulse wave velocity of 0.103 m/s.

Conclusions We found that a high level of pedometer-determined physical activity was associated with a slower progression of arterial stiffness over 4 years in middle-aged people with Type 2 diabetes.

Necrotizing enterocolitis (NEC) is a devastating intestinal disease in preterm infants characterized by barrier disruption, intestinal microbial dysbiosis, and persistent inflammation of the colon, which results in high mortality rates. Current strategies used to manage this disease are not sufficient, although the use of human breast milk reduces the risk of NEC. Mothers milk is regarded as a fundamental nutritional source for neonates, but pasteurization of donor breast milk affects the composition of bioactive compounds. Current research is evaluating the benefits and potential pitfalls of adding probiotics and prebiotics to pasteurized milk so as to improve the functionality of the milk and thereby reduce the burden of illness caused by NEC. Probiotics (live micro-organisms that confer health to the host) and prebiotics (nondigestible oligosaccharides that stimulate the growth of healthy bacteria) are functional foods known to mediate immune responses and modulate microbial populations in the gut. Clinical research shows strain-and compound specific responses when probiotics or prebiotics are administered in conjunction with donor breast milk for the prevention of NEC. Despite ongoing controversy surrounding optimal treatment strategies, randomized controlled studies are now investigating the use of synbiotics to reduce the incidence and severity of NEC. Synbiotics, a combination of probiotics and prebiotics, have been proposed to enhance beneficial health effects in the intestinal tract more than either agent administered alone. This review considers the implications of using probiotic-, prebiotic-, and synbiotic-supplemented breast milk as a strategy to prevent NEC and issues that could be encountered with the preparations.

CONTEXT: Screening of autoimmune thyroid disease in children and young adults with Type 1 diabetes is important but vary greatly between clinics.

OBJECTIVE: The aim was to determine the predictive value of thyroid autoantibodies, thyroid function, islet autoantibodies, and HLA- DQ at diagnosis of Type 1 diabetes for autoimmune thyroid disease during subsequent follow-up.

SETTING: 43 Paediatric Endocrinology units Sweden. Design, patients and main outcome measures: At diagnosis of Type 1 diabetes, samples from 2433 children were analysed for autoantibodies against thyroid peroxidase (TPOAb), thyroglobulin (TGAb), glutamic acid decarboxylase (GADA), insulin (IAA), insulinoma-associated protein-2 (IA-2A), and the three variants of the zinc transporter 8 (ZnT8W/R/QA) as well as HLA-DQA1-B1 genotypes and thyroid function. After 5.1-9.5 years disease duration, children treated with thyroxine were identified in the Swedish National Board of Health and Welfare Prescribed Drug Register.

RESULTS: Thyroxine had been prescribed to 6% (147/2433; 66% girls). In patients below 5 years, female gender (HR=4.60, p=0.008) and GADA (HR=5.80, p=0.02) were significant predictors. In patients 5-10 years, TPOAb (HR=20.56, p<0.0001), TGAb (HR=3.40, p=0.006) and TSH outside the reference limit (HR=3.64, p<0.001) were predictors while in the 10-15 year olds, TPOAb (HR=17.00, p<0.001) and TSH outside the reference limit (HR=4.11, p<0.001) predicted future thyroxine prescription.

CONCLUSION: In addition to TPOAb and TSH, positive GADA tested at the diagnosis of type 1 diabetes is important for the prediction of autoimmune thyroid disease in children below 5 years of age.

BACKGROUND: Early psychosocial exposures are increasingly recognized as being crucial to health throughout life. A possible mechanism could be physiologic dysregulation due to stress. Cortisol in hair is a new biomarker assessing long-term hypothalamic-pituitary-adrenal axis activity. The objective was to investigate whether early-life adverse psychosocial circumstances influence infant cortisol levels in hair and health outcomes in children prospectively until age 10. METHODS: A cohort study in the general community using a questionnaire covering 11 psychosocial items in the family during pregnancy and the cumulative incidence of diagnoses until age 10 years in 1876 children. Cortisol levels in hair were measured by using a radioimmunoassay in those with sufficient hair samples at age 1, yielding a subsample of n = 209. RESULTS: Children with added psychosocial exposures had higher infant cortisol levels in hair (B = 0.40, P less than .0001, adjusted for gender and size for gestational age) in a cumulative manner and were significantly more often affected by 12 of the 14 most common childhood diseases, with a general pattern of increasing odds ratios. CONCLUSIONS: The findings support the model of physiologic dysregulation as a plausible mechanism by which the duration and number of early detrimental psychosocial exposures determine health outcomes. The model indicates that the multiplicity of adversities should be targeted in future interventions and could help to identify children who are at high risk of poor health. Furthermore, given the prolonged nature of exposure to a stressful social environment, the novel biomarker of cortisol in hair could be of major importance.

Background: Pediatric T-cell acute lymphoblastic leukemia (T-ALL) is a genetically heterogeneous disease that arises in a multistep fashion through acquisition of several genetic aberrations, subsequently giving rise to a malignant, clonal expansion of T-lymphoblasts. The aim of the present study was to identify additional as well as cooperative genetic events in T-ALL. Methods: A population-based pediatric T-ALL series comprising 47 cases was investigated by SNP array and deep sequencing analyses of 75 genes, in order to ascertain pathogenetically pertinent aberrations and to identify cooperative events. Results: The majority (92%) of cases harbored copy number aberrations/uniparental isodisomies (UPIDs), with a median of three changes (range 0-11) per case. The genes recurrently deleted comprised CDKN2A, CDKN2B, LEF1, PTEN, RBI, and STIL. No case had a whole chromosome UPID; in fact, literature data show that this is a rare phenomenon in T-ALL. However, segmental UPIDs (sUPIDs) were seen in 42% of our cases, with most being sUPID9p that always were associated with homozygous CDKN2A deletions, with a heterozygous deletion occurring prior to the sUPID9p in all instances. Among the 75 genes sequenced, 14 (19%) were mutated in 28 (72%) of 39 analyzed cases. The genes targeted are involved in signaling transduction, epigenetic regulation, and transcription. In some cases, NOTCH1 mutations were seen in minor subclones and lost at relapse; thus, such mutations can be secondary events. Conclusions: Deep sequencing and SNP array analyses of T-ALL revealed lack of wUPIDs, a high proportion of sUPID9p targeting CDKN2A, NOTCH1 mutations in subclones, and recurrent mutations of genes involved in signaling transduction, epigenetic regulation, and transcription.

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.

OBJECTIVE: To describe the introduction of complementary foods in a population-based cohort in relation to recommendations and explore the possible impact of maternal education on infant feeding practices.

DESIGN: Prospective data from the All Babies in Southeast Sweden (ABIS) cohort study were used. The ABIS study invited all infants born in south-east Sweden during October 1997-October 1999 (n 21 700) to participate. A questionnaire was completed for 16 022 infants. During the infants' first year parents continuously filed in a diary covering introduction of foods.

SETTING: Sweden.

SUBJECTS: Infants (n 9727) with completed food diaries.

RESULTS: Potatoes, vegetables, fruits/berries and porridge were the foods first introduced, with a median introduction between 19 and 22 weeks, followed by introduction of meat, cow's milk, follow-on formula and sour milk/yoghurt between 24 and 27 weeks. Early introduction of any food, before 16 weeks, occurred for 27 % of the infants and was more common in infants of mothers with low education. Overall, potatoes (14·7 %), vegetables (11·1 %), fruits/berries (8·5 %), porridge (7·4 %) and follow-on formula (2·7 %) were the foods most frequently introduced early. The majority of infants (≥70 %) were introduced to potatoes, vegetables, fruits/berries and porridge during concurrent breast-feeding, but introduction during concurrent breast-feeding was less common in infants of mothers with low education.

CONCLUSIONS: Most infants were introduced to complementary foods timely in relation to recommendations. Low maternal education was associated with earlier introduction of complementary foods and less introduction during concurrent breast-feeding. Still, the results indicated exposure to fewer foods at 12 months in infants of mothers with low education.

The understanding of the etiology of type 1 diabetes (T1D) remains limited. One objective of the Diabetes Virus Detection (DiViD) study was to collect pancreatic tissue from living subjects shortly after the diagnosis of T1D. Here we report the insulin secretion ability by in vitro glucose perifusion and explore the expression of insulin pathway genes in isolated islets of Langerhans from these patients. Whole-genome RNA sequencing was performed on islets from six DiViD study patients and two organ donors who died at the onset of T1D, and the findings were compared with those from three nondiabetic organ donors. All human transcripts involved in the insulin pathway were present in the islets at the onset of T1D. Glucose-induced insulin secretion was present in some patients at the onset of T1D, and a perfectly normalized biphasic insulin release was obtained after some days in a nondiabetogenic environment in vitro. This indicates that the potential for endogenous insulin production is good, which could be taken advantage of if the disease process was reversed at diagnosis.

Background: Patients with celiac disease (CD) often have articular complaints, and small prior studies suggest an association with Ehlers-Danlos syndrome (EDS)/joint hypermobility syndrome (JHS). Aims: This study examines the risks of EDS/JHS in patients with CD. Methods: This cohort study compared all individuals in Sweden diagnosed with CD based on small intestinal biopsy between 1969-2008 (n = 28,631) to 139,832 matched reference individuals, and to a second reference group undergoing biopsy without having CD (n = 16,104). Rates of EDS/JHS were determined based on diagnostic codes in the Swedish Patient Register. Hazard ratios (HRs) for EDS/JHS were estimated through Cox regression. Results: There are 45 and 148 cases of EDS/JHS in patients with CD and reference individuals, respectively. This corresponds to a 49% increased risk of EDS/JHS in CD (95% CI = 1.07-2.07). The HR for EDS was 2.43 (95% CI = 1.20-4.91) and for JHS 1.34 (95% CI = 0.93-1.95). Compared to reference individuals undergoing intestinal biopsy, CD was not a risk factor for EDS/JHS. A stronger association was seen in patients initially diagnosed with EDS/JHS and subsequently diagnosed with CD (odds ratio = 2.29; 95% CI = 1.21-4.34). Conclusions: Individuals with CD have higher risk of EDS/JHS than the general population, which may be due to surveillance bias or factors intrinsic to celiac development. (C) 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

AimThis Swedish study compared reading skills between seven-year-old children with a very low birthweight (VLBW) and controls with a normal birthweight, exploring associations between reading variables and cognition, parent-rated behaviour, perinatal factors and family factors. MethodsWe studied 51 VLBW children, with no major neurodevelopmental impairments and attending their first year at a regular school, and compared them with the 51 sex- and age-matched controls. The test battery, carried out at 7.80.4years of age, included reading skills, the Wechsler Intelligence Scale for Children - III and the Child Behaviour Checklist. ResultsVery low birthweight children with a mean birthweight of 1105g (+/- 291g) and a gestational age of 28.8 (+/- 2.2) weeks scored significantly lower in all reading subtests and cognition and demonstrated more behavioural problems than normal birthweight controls. We also found significant associations between poor vocabulary, combined with attention problems, and phonological awareness, rapid naming and spelling control. Perinatal factors had no association with reading function, and socio-economic factors had very few. ConclusionVery low birthweight children demonstrated deficits in all reading domains and had poorer cognition and more behavioural problems at the age of seven, with reading ability related to vocabulary and attention.

Highly prevalent and typically beginning in childhood, asthma is a burdensome disease, yet the risk factors for this condition are not clarified. To enhance understanding, this study assessed the cohort-specific and pooled risk of maternal education on asthma in children aged 3-8 across 10 European countries. Data on 47,099 children were obtained from prospective birth cohort studies across 10 European countries. We calculated cohort-specific prevalence difference in asthma outcomes using the relative index of inequality (RII) and slope index of inequality (SII). Results from all countries were pooled using random-effects meta-analysis procedures to obtain mean RII and SII scores at the European level. Final models were adjusted for child sex, smoking during pregnancy, parity, mothers age and ethnicity. The higher the score the greater the magnitude of relative (RII, reference 1) and absolute (SII, reference 0) inequity. The pooled RII estimate for asthma risk across all cohorts was 1.46 (95% CI 1.26, 1.71) and the pooled SII estimate was 1.90 (95% CI 0.26, 3.54). Of the countries examined, France, the United Kingdom and the Netherlands had the highest prevalences of childhood asthma and the largest inequity in asthma risk. Smaller inverse associations were noted for all other countries except Italy, which presented contradictory scores, but with small effect sizes. Tests for heterogeneity yielded significant results for SII scores. Overall, offspring of mothers with a low level of education had an increased relative and absolute risk of asthma compared to offspring of high-educated mothers.

The heterogeneity of atherosclerotic tissue has limited comprehension in proteomic and metabolomic analyses. To elucidate the functional implications, and differences between genders, of atherosclerotic lesion formation we investigated protein profiles from different regions of human carotid atherosclerotic arteries; internal control, fatty streak, plaque shoulder, plaque centre, and fibrous cap. Proteomic analysis was performed using 2-DE with MALDI-TOF, with validation using nLC-MS/MS. Protein mapping of 2-DE identified 52 unique proteins, including 15 previously unmapped proteins, of which 41 proteins were confirmed by nLC-MS/MS analysis. Expression levels of 18 proteins were significantly altered in plaque regions compared to the internal control region. Nine proteins showed site-specific alterations, irrespective of gender, with clear associations to extracellular matrix remodelling. Five proteins display gender-specific alterations with 2-DE, with two alterations validated by nLC-MS/MS. Gender differences in ferritin light chain and transthyretin were validated using both techniques. Validation of immunohistochemistry confirmed significantly higher levels of ferritin in plaques from male patients. Proteomic analysis of different plaque regions has reduced the effects of plaque heterogeneity, and significant differences in protein expression are determined in specific regions and between genders. These proteomes have functional implications in plaque progression and are of importance in understanding gender differences in atherosclerosis.

Fusion genes are potent driver mutations in cancer. In this study, we delineate the fusion gene landscape in a consecutive series of 195 paediatric B-cell precursor acute lymphoblastic leukaemia (BCP ALL). Using RNA sequencing, we find in-frame fusion genes in 127 (65%) cases, including 27 novel fusions. We describe a subtype characterized by recurrent IGH-DUX4 or ERG-DUX4 fusions, representing 4% of cases, leading to overexpression of DUX4 and frequently co-occurring with intragenic ERG deletions. Furthermore, we identify a subtype characterized by an ETV6-RUNX1-like gene-expression profile and coexisting ETV6 and IKZF1 alterations. Thus, this study provides a detailed overview of fusion genes in paediatric BCP ALL and adds new pathogenetic insights, which may improve risk stratification and provide therapeutic options for this disease.

Background and aims: In patients with type 1 diabetes mellitus (T1D), cardiovascular disease (CVD) events are more common and occur earlier in life than in non-diabetics. Reduced brachial artery distensibility (BrachD) is an independent risk factor for development of CVD. Our aim was to determine if adults with T1D have lower BrachD compared to adults without diabetes and also to determine how age and gender affect the relationship of BrachD with T1D status. Materials and methods: BrachD was measured using the Dynapulse instrument in 829 participants (352 with T1D, 477 non-diabetics). An ANCOVA model was used to test the association of BrachD with age, sex, and T1D, and the significance of an age*sex*T1D interaction. Results: Mean BrachD was lower in T1D patients vs. controls (6.43 +/- 1.46 vs. 7.16 +/- 1.48 % change per mmHg, p amp;lt; 0.0001). In a model adjusted for age, T1D, and sex, the interaction of age*T1D*sex was significant (p = 0.0045). Younger women both with and without T1D had higher BrachD than men with and without T1D, but older women with and without T1D had lower BrachD compared to older men with and without T1D. Women with T1D had a steeper decline in BrachD with age than nondiabetic women. Conclusions: BrachD is lower in T1D patients than in non-diabetics, indicating increased vascular stiffness. Younger females have higher BrachD than males, but the decline with age in BrachD is steeper for women, particularly among those with T1D. BrachD may be an inexpensive, non-invasive method to ascertain increased CVD risk in this population. (C) 2016 Elsevier Inc. All rights reserved.

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