Skin Reactions in Children with Type 1 Diabetes Associated with the Use of New Diabetes Technologies-An Observational Study from a Regional Polish Pediatric Diabetes Center.

The study aimed to estimate the prevalence of skin problems in children and adolescents with type 1 diabetes (T1D) using insulin pumps (IPs) and/or continuous glucose monitoring (CGM) in our center and analyze their association with various factors. As part of the international ISPAD JENIOUS-initiated SKIN-PEDIC project, we interviewed and examined patients who visited the regional pediatric diabetes center in Opole (Poland) for four weeks regarding the use of IP and/or CGM and the presence of skin problems. Body mass index (BMI) and glycemic parameters were obtained retrospectively from medical records. Among 115 individuals (45.2% girls, 83.5% IP users, 96.5% CGM users), old scars were the most common skin problem (IP users 53.1%; CGM users 66.4%), while ≥2 types of skin problems co-occurred (IP users 40.6%; CGM users 27.3%). Longer IP use was associated with a higher prevalence of skin problems (50% for IP < 1 year, 98.1%-IP 1-3 years, 100% for IP > 3 years; p < 0.001), pointing out extra attention with IP use > 1 year. No significant associations were found between skin problems and gender, age, BMI centile and glycemic parameters. Dermatological complications were common among children using IP and CGM in our center, highlighting the need for vigilant monitoring and early intervention to manage these skin-related issues effectively.

The effect of stress on the antibody response after vaccination in children aged 0-18 years: A systematic review.

Stress has been associated with less effective vaccine responses in adults. This review aims to investigate the evidence for a similar association in children. A systematic review search was conducted in January 2021 in three databases: Medline, Embase and PsycInfo. An updated search of the Medline database was systematically conducted until the most recent update on September 25th, 2023, to ensure the inclusion of the most current research available. Keywords related to stress, vaccines and children were used, and a total of 7263 (+1528) studies were screened by two independent investigators. Six studies met the inclusion criteria for data extraction and analysis. For quality assessment of the studies, the risk of bias in non-randomized studies-of interventions (ROBINS-I) tool was applied. Most of the studies suggest a negative role of stress on vaccine responses. However, the scarcity of studies, lack of confirmatory studies, risk of bias and heterogeneity according to age, type of vaccine, measures of stress and vaccine responses prevent a clear conclusion. Future studies should emphasize the use of as strict study designs as possible, including well-defined stress metrics and thorough examination of both pre- and post-vaccination responses. Systematic review registration: Prospero CRD42021230490.

The risk of Type 1 diabetes in children born after ART: a Nordic cohort study from the CoNARTaS group.

STUDY QUESTION: Do children born after ART have a higher risk of developing Type 1 diabetes (DM1) than children conceived without ART? SUMMARY ANSWER: The risk of DM1 was similar for children conceived with and without ART, and there were no clear differences in risk according to method of fertility treatment. WHAT IS KNOWN ALREADY: ART is associated with a higher risk of adverse perinatal outcomes, and the risk depends on the method of ART. The Developmental Origins of Health and Disease theory proposes that prenatal stress can provoke changes in endocrine processes which impact health later in life. STUDY DESIGN SIZE DURATION: A Nordic register-based cohort study was carried out, including all children born in Denmark (birth years 1994-2014), Finland (1990-2014), and Norway (1984-2015). The study included 76 184 liveborn singletons born after ART and 4 403 419 born without ART. Median follow-up was 8.3 and 13.7 years in the ART and non-ART group, respectively. PARTICIPANTS/MATERIALS SETTING METHODS: The cohort, initiated by the Committee of Nordic Assisted Reproductive Technology and Safety (CoNARTaS), was established by linking national registry data from the medical birth registries and national patient registries available in the Nordic countries. We performed multivariable logistic regression analyses for the birth year intervals 1984-1990, 1991-1995, 1996-2000, 2001-2005, 2006-2010, and 2011-2015, while adjusting for year of birth within each interval, sex of the child, parity, maternal age, maternal diabetes, and maternal smoking during pregnancy as potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE: During follow-up, 259 (3.4‰) children born after ART were diagnosed with DM1, while this was the case for 22 209 (5.0‰) born without ART, corresponding to an adjusted odds ratio of 0.98 (95% CI: 0.861.11). Within the different birth year intervals, no significant difference in risk of DM1 between the two groups was found, except for the youngest cohort of children born 2011-2015 where ART was associated with a higher risk of DM1. We found no significant differences in risk of DM1 when comparing children born after IVF versus ICSI or fresh versus frozen embryo transfer, but with only few cases in each group. LIMITATIONS REASONS FOR CAUTION: The main limitation of the study is the relatively short follow-up time. The incidence rate of DM1 peaks during ages 10-14 years, hence a longer follow-up would benefit all analyses and, in particular, the subgroup analyses. WIDER IMPLICATIONS OF THE FINDINGS: Overall, our findings are reassuring especially considering the concomitantly increasing number of children born from ART and the increasing incidence of DM1 globally. STUDY FUNDING/COMPETING INTERESTS: This Nordic registry study has been supported by the Nordic Trial Alliance/NORDFORSK and Rigshospitalets Research Foundation. The funding sources had no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. None of the authors has any conflicts of interest to declare regarding this study. TRIAL REGISTRATION NUMBER: ISRCTN11780826.

Impact of Missed and Late Meal Boluses on Glycemic Outcomes in Automated Insulin Delivery-Treated Children and Adolescents with Type 1 Diabetes: A Two-Center, Population-Based Cohort Study.

Objective: To evaluate the impact of missed or late meal boluses (MLBs) on glycemic outcomes in children and adolescents with type 1 diabetes using automated insulin delivery (AID) systems. Research Design and Methods: AID-treated (Tandem Control-IQ or Medtronic MiniMed 780G) children and adolescents (aged 6-21 years) from Stanford Medical Center and Steno Diabetes Center Copenhagen with ≥10 days of data were included in this two-center, binational, population-based, retrospective, 1-month cohort study. The primary outcome was the association between the number of algorithm-detected MLBs and time in target glucose range (TIR; 70-180 mg/dL). Results: The study included 189 children and adolescents (48% females with a mean ± standard deviation age of 13 ± 4 years). Overall, the mean number of MLBs per day in the cohort was 2.2 ± 0.9. For each additional MLB per day, TIR decreased by 9.7% points (95% confidence interval [CI] 11.3; 8.1), and compared with the quartile with fewest MLBs (Q1), the quartile with most (Q4) had 22.9% less TIR (95% CI: 27.2; 18.6). The age-, sex-, and treatment modality-adjusted probability of achieving a TIR of >70% in Q4 was 1.4% compared with 74.8% in Q1 (P < 0.001). Conclusions: MLBs significantly impacted glycemic outcomes in AID-treated children and adolescents. The results emphasize the importance of maintaining a focus on bolus behavior to achieve a higher TIR and support the need for further research in technological or behavioral support tools to handle MLBs.

Pressure pain sensitivity: A new stress measure in children and adolescents with type 1 diabetes?

Type 1 diabetes (T1D) is associated with general- and diabetes-specific stress which has multiple adverse effects. Hence measuring stress is of great importance. An algometer measuring pressure pain sensitivity (PPS) has been shown to correlate to certain stress measures in adults. However, it has never been investigated in children and adolescents. The aim of our study was to examine associations between PPS and glycated hemoglobin (HbA1c), salivary cortisol and two questionnaires as well as to identify whether the algometer can be used as a clinical tool among children and adolescents with T1D. Eighty-three participants aged 6-18 years and diagnosed with T1D were included in this study with data from two study visits. Salivary cortisol, PPS and questionnaires were collected, measured, and answered on site. HbA1c was collected from medical files. We found correlations between PPS and HbA1c (rho = 0.35, P = 0.046), cortisol (rho = -0.25, P = 0.02) and Perceived Stress Scale (rho = -0.44, P = 0.02) in different subgroups based on age. Males scored higher in PPS than females (P < 0.001). We found PPS to be correlated to HbA1c but otherwise inconsistent in results. High PPS values indicated either measurement difficulties or hypersensibility towards pain.

The role of sex on the prevalence of cardiovascular risk factors in children and adolescents with Type 1 diabetes: The SWEET international database.

OBJECTIVE: To assess the prevalence of cardiovascular risk factors (CVRFs) in children and adolescents with type 1 diabetes (T1D) in the International SWEET registry and the possible role of clinical variables in modifying the risk of having single or multiple CVRFs. STUDY DESIGN: The study is a cross-sectional study. Cut-off points for CVRFs were fixed according to International Society for Pediatric and Adolescent Diabetes (ISPAD) guidelines and WHO parameters: LDL cholesterol (LDL-C) > 100 mg/dL; Systolic Blood Pressure (BP-SDS) > 90th percentile for sex, age, and height; BMI-SDS > 2SD for sex and age. Logistic regression models were applied to evaluate variables associated with at least 1 or 2 CVRFs among registry children and adolescents. RESULTS: 29,649 individuals with T1D (6-18 years, T1D ≥ 2 years) participating in the SWEET prospective multicenter diabetes registry were included. In the cohort, 41 % had one or more CVRFs, and 10 % had two or more CVRFs. Thirty-five percent of enrolled individuals had LDL-C > 100 mg/dL, 26 % had BMI-SDS > 2SD, and 17 % had Systolic BP-SDS > 90th percentile. Females had higher frequency than males of having 1 or 2 CVRFs (45.1 % vs 37.4 %, 11.8 % vs 7.8 %; p < 0.001). Multivariable logistic regression models showed that sex (female), HbA1c category (>7.0 %), and age (>10 years) were associated with a higher chance of having at least 1 or 2 CVRFs (p < 0.001). CONCLUSIONS: In children and adolescents with T1D, female sex, in addition to HbA1c above 7 %, and older age (>10 years) was associated with a higher risk of having at least a CVRF (LDL-C, BMI-SDS, BP) according to internationally defined cut-offs.

No association between long-chain n-3 fatty acid intake during pregnancy and risk of type 1 diabetes in offspring in two large Scandinavian pregnancy cohorts.

AIMS/HYPOTHESIS: The aim of this study was to investigate whether higher dietary intake of marine n-3 fatty acids during pregnancy is associated with a lower risk of type 1 diabetes in children. METHODS: The Danish National Birth Cohort (DNBC) and the Norwegian Mother, Father and Child Cohort Study (MoBa) together include 153,843 mother-child pairs with prospectively collected data on eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intake during pregnancy from validated food frequency questionnaires. Type 1 diabetes diagnosis in children (n=634) was ascertained from national diabetes registries. RESULTS: There was no association between the sum of EPA and DHA intake during pregnancy and risk of type 1 diabetes in offspring (pooled HR per g/day of intake: 1.00, 95% CI 0.88, 1.14), with consistent results for both the MoBa and the DNBC. Robustness analyses gave very similar results. CONCLUSIONS/INTERPRETATION: Initiation of a trial of EPA and DHA during pregnancy to prevent type 1 diabetes in offspring should not be prioritised.

Immunogenicity and reactogenicity following MMR vaccination in 5-7-month-old infants: a double-blind placebo-controlled randomized clinical trial in 6540 Danish infants.

Background: Measles is a highly contagious viral disease. Vaccinated mothers transfer fewer antibodies during pregnancy, resulting in shortened infant immunity. Earlier primary vaccination might avert the gap in protection. Methods: Healthy 5-7-month-old Danish infants were assigned in a 1:1 ratio to M-M-RVaxPro or placebo (solvent) in a double-blind, randomized trial between April 15, 2019 and November 1, 2021 (ClinicalTrials.govNCT03780179, EudraCT 2016-001901-18). Eligibility criteria were birth weight >1000 g and gestational age ≥32 weeks.Immunogenicity was measured by plaque reduction neutralization test (PRNT) and IgG ELISA before intervention, four weeks after intervention and routine MMR. Reactogenicity data were collected for six weeks and measured by hazard ratios (HR). Findings: 647 and 6540 infants participated in the immunogenicity and reactogenicity study, respectively; 87% and 99% completed follow-up. After early MMR, seroprotection rates (SPRs) were 47% (13%) in measles PRNT; 28% (2%), 57% (8%) in mumps and rubella IgG (placebo). For measles PRNT, geometric mean ratio was 4.3 (95% CI: 3.4-5.3) between randomization groups after intervention and 1.5 (95% CI: 1.3-1.9) after routine MMR.Reactogenicity was independent of randomization (HR, 1.0; 95% CI: 0.9-1.1). Severe adverse events occurred in 25 infants (HR, 1.8; 95% CI: 0.8-4.0); none deemed vaccine related. Interpretation: Early MMR elicited low SPRs but did not negatively impact short-term responses to a subsequent MMR. MMR at 5-7 months was safe and not associated with higher rates of reactogenicity than placebo. Funding: Innovation Fund Denmark.

Heterogeneity in glycaemic control in children and adolescents with type 1 diabetes: A latent class trajectory analysis of Danish nationwide data.

AIMS: Suboptimal glycaemic control in children and adolescents with type 1 diabetes is prevalent and associated with increased risk of diabetes-related complications and mortality later in life. First, we aimed to identify distinct glycated haemoglobin (HbA1c) trajectories in children and adolescents (2-19 years) with type 1 diabetes. Second, we examined their associations with clinical and socio-demographic factors. METHODS: Data were obtained from the Danish Registry of Childhood and Adolescent Diabetes (DanDiabKids) comprising all Danish children and adolescents diagnosed with type 1 diabetes from 1996 to 2019. Subgroups of distinct mean trajectories of HbA1c were identified using data-driven latent class trajectory modelling. RESULTS: A total of 5889 children (47% female) had HbA1c measured a median of 6 times (interquartile range 3-8) and contributing to 36,504 measurements. We identified four mean HbA1c trajectories, referred to as 'Stable but elevated HbA1c' (83%), 'Increasing HbA1c' (5%), 'Late HbA1c peak' (7%), and 'Early HbA1c peak' (5%). Compared to the 'Stable but elevated HbA1c' group, the three other groups presented rapidly deteriorating glycaemic control during late childhood or adolescence, had higher HbA1c at study entry, and included fewer pump users, higher frequency of inadequate blood glucose monitoring, more severe hypoglycaemic events, lower proportions with Danish origin, and worse educational status of parents. The groups also represented significant differences by healthcare region. CONCLUSIONS: Children and adolescents with type 1 diabetes experience heterogenous trajectories with different timings and magnitudes of the deterioration of HbA1c levels, although the majority follow on average a stable, yet elevated HbA1c trajectory. The causes and long-term health implications of these heterogenous trajectories need to be addressed.

No associations between type 1 diabetes and atopic dermatitis, allergic rhinitis, or asthma in childhood: a nationwide Danish case-cohort study.

Studies examining the association between type 1 diabetes (T1D) and atopic diseases, i.e., atopic dermatitis, allergic rhinitis and asthma have yielded conflicting results due to different algorithms for classification, sample size issues and risk of referral bias of exposed cohorts with frequent contact to health care professionals. Using Danish national registries and well-established disease algorithms, we examined the bidirectional association between T1D and atopic diseases in childhood and adolescence using Cox Proportional Hazard regression compared to two different unexposed cohorts from a population of 1.5 million Danish children born from 1997 to 2018. We found no associations between T1D and atopic dermatitis, allergic rhinitis, or asthma (defined after age five). However, in multivariable analysis we found an increased risk of persistent wheezing (defined as asthma medication before age five) after T1D with an adjusted hazard ratio (aHR) of 1.70 [1.17-2.45]. We also identified an increased risk of developing T1D after persistent wheezing with aHR of 1.24 [1.13-1.36]. This study highlights similar risks of atopic diseases in children with T1D and of T1D in children with atopic disease after age of five years versus healthy controls. However, more research is needed to understand the possible early immunological effects of the link between persistent wheezing and T1D.

Validation of the newly developed Sleep Screening Questionnaire Children and Adolescents (SSQ-CA) with objective sleep measures.

OBJECTIVES: Objectively validated pediatric sleep questionnaires covering a broader age range and different sleep disturbances are lacking, therefore we developed the Sleep Screening Questionnaire Children and Adolescents (SSQ-CA) and compared it with objective sleep parameters. METHODS: This child-reported questionnaire was developed by a multidisciplinary panel and face validated. In a cross-sectional prospective design, participants aged 6-17, answered the questionnaire twice with 21-28 days in between, wore actigraphy (AG) and kept a sleep diary for seven nights and home-polysomnography (PSG) for one of these nights. Exploratory factor analyses (EFA), reliability and validity assessments were performed. RESULTS: Of the 139 participants, 128 (F:47.7%, AG: n = 128, PSG: n = 59), were included in the analyses. Mean age: 11.3 years (SD: 2.9). EFA revealed 11 factors and 40 items loading above r = 0.4. Subscale internal consistency: 0.54-0.92. Subscale test-retest reliability: r = 0.71-0.87. Total sleep time (TST) from SSQ-CA on weekdays correlated with PSG (r = 0.48, p = 0.001) and with AG (r = 0.75, p < 0.001). The subscale total score for "Sleep duration and latency" correlated with TST from AG (r = -0.19, p = 0.03) and sleep latency (r = 0.31, p < 0.001), but not for PSG variables. The subscale "Awakenings" showed no correlation with objective measures whereas "Circadian rhythm" correlated to AG-derived mid-sleep time (r = 0.34, p < 0.001). CONCLUSIONS: The SSQ-CA shows adequate reliability for the 6-17-year-olds and acceptable criterion validity for two subscales. It appears to be a useful tool for screening for sleep disturbances in combination with objective tools as the subjective and objective parameters seem to uncover different aspects of sleep.

Glucose Monitoring Metrics in Individuals With Type 1 Diabetes Using Different Treatment Modalities: A Real-World Observational Study.

OBJECTIVE: This study aimed to investigate the association between continuous glucose monitoring (CGM)-derived glycemic metrics and different insulin treatment modalities using real-world data. RESEARCH DESIGN AND METHODS: A cross-sectional study at Steno Diabetes Center Copenhagen, Denmark, included individuals with type 1 diabetes using CGM. Data from September 2021 to August 2022 were analyzed if CGM was used for at least 20% of a 4-week period. Individuals were divided into four groups: multiple daily injection (MDI) therapy, insulin pumps with unintegrated CGM (SUP), sensor-augmented pumps with low glucose management (SAP), and automated insulin delivery (AID). The MDI and SUP groups were further subdivided based on CGM alarm features. The primary outcome was percentage of time in range (TIR: 3.9-10.0 mmol/L) for each treatment group. Secondary outcomes included other glucose metrics and HbA1c. RESULTS: Out of 6,314 attendees, 3,184 CGM users were included in the analysis. Among them, 1,622 used MDI, 504 used SUP, 354 used SAP, and 561 used AID. Median TIR was 54.0% for MDI, 54.9% for SUP, 62,9% for SAP, and 72,1% for AID users. The proportion of individuals achieving all recommended glycemic targets (TIR >70%, time above range <25%, and time below range <4%) was significantly higher in SAP (odds ratio [OR] 2.4 [95% CI 1.6-3.5]) and AID (OR 9.4 [95% CI 6.7-13.0]) compared with MDI without alarm features. CONCLUSIONS: AID appears superior to other insulin treatment modalities with CGM. Although bias may be present because of indications, AID should be considered the preferred choice for insulin pump therapy.

Lipohypertrophy and Insulin: An Update From the Diabetes Technology Society.

Lipohypertrophy is a common skin complication associated with insulin-treated diabetes. The impact of lipohypertrophy as a contributing factor to suboptimal glycemic control, glucose variability, and hypoglycemia is often under-recognized by health care professionals. In a recent Webinar on April 26, 2023, Diabetes Technology Society asked international experts to provide updates on the latest knowledge related to lipohypertrophy for practicing clinicians and educators, researchers, and industries involved in insulin delivery. A recording of the Webinar is freely available on the Diabetes Technology Society Web site (https://www.diabetestechnology.org/).

A Skin Care Program to Prevent Skin Problems due to Diabetes Devices in Children and Adolescents: A Cluster-Controlled Intervention Study.

OBJECTIVE: Diabetes devices that deliver insulin and measure blood glucose levels are cornerstones in modern treatment of type 1 diabetes. However, their use is frequently associated with the development of skin problems, particularly eczema and wounds. Proper skin care may prevent skin problems, yet evidence-based information from interventional studies is missing. Providing this information is the aim of this study. RESEARCH DESIGN AND METHODS: This cluster-controlled intervention study tested the efficacy of a basic skin care program (including use of lipid cream, removal, and avoidance of disinfection). A total of 170 children and adolescents with type 1 diabetes were included and assigned either to the intervention group (n = 112) or the control group (n = 58). Participants were seen quarterly the first year after device initiation, with clinical assessment and interview in an unblinded setting. RESULTS: Eczema or wounds were observed in 33.6% of the intervention group compared with 46.6% of control participants (absolute difference, 12.9% [95% CI -28.7%, 2.9%]; P = 0.10). The adjusted odds of wound development were decreased by 71% in the intervention compared with control group (for wounds, odds ratio 0.29 [95% CI 0.12, 0.68]; P = 0.005). In total, only eight infections were seen, without a higher frequency in the intervention group, despite advice to omit disinfection. CONCLUSIONS: These data indicate our basic skin care program partially prevented diabetes device-induced skin reactions. However, more preventive strategies with other adhesives, patches, and/or types of lotions are needed for optimized prevention.

An Occlusive Hydrocolloid-Based Patch Is Effective, Feasible, and Safe As a Treatment of Irritant Contact Dermatitis Due to Diabetes Devices in Children and Adolescents with Type 1 Diabetes.

Irritant contact dermatitis (ICD) occurs frequently with the use of diabetes devices, but no guidelines for treatment exist. Since subsequent devices need intact skin for intended use, quick healing is crucial. Normal wound healing is expected to be 7-10 days. This was a single-center cross-over study that investigated the effectiveness of an occlusive hydrocolloid-based patch versus nonocclusive treatment of ICD. Participants were aged 6-20 years with active ICD caused by using diabetes device. First study period was patch treatment for 3 days. A control arm was initiated if a new ICD occurred within 30 days. ICD healed completely in 21% of the patch group but none in the controls. Itching was reported as an adverse event (AE) in both arms, but only one additional AE was noted in the patch arm: an infection at a different site from investigated. The hydrocolloid-based patch showed signs of faster healing of ICD with no additional AEs, but larger studies are needed.

Ultrasound Detected Subcutaneous Changes in a Pediatric Cohort After Initiation of a New Insulin Pump or Glucose Sensor.

Objective: This study examined subcutaneous tissue changes at sites used by continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM), and tested whether these changes, if any, were associated with glycated hemoglobin (HbA1c). Research Design and Methods: This prospective study investigated recently used CSII or CGM sites in 161 children and adolescents during the first year after initiation of a new diabetes device. Subcutaneous changes such as echogenicity, vascularization, and the distance from the skin surface to the muscle at CSII and CGM sites were assessed by ultrasound. Results: The distance from skin surface to muscle fascia at both the upper arm and abdomen was influenced by age, body mass index z-score, and sex. Especially in boys and the youngest, the depth of many devices outreached the mean distance. The mean distance for boys at the abdomen and upper arm ranged from 4.5-6.5 mm and 5-6.9 mm for all ages, respectively. Hyperechogenicity at CGM sites was 4.3% after 12 months. The frequency of subcutaneous hyperechogenicity and vascularization at CSII sites increased significantly over time (41.2% to 69.3% and 2% to 16% respectively, P < 0.001 and P = 0.009). Hyperechogenicity in the subcutis was not a predictor of elevated HbA1c (P = 0.11). Conclusion: There is large variation in the distance from the skin surface to the muscle fascia and many diabetes devices reach even deeper. Hyperechogenicity and vascularization increased significantly over time at CSII sites, but not CGM sites. The importance of hyperechogenicity for insulin absorption is unclear and further investigations are needed. Clinical Trial Registration number: NCT04258904.

Measles, mumps, and rubella vaccine at age 6 months and hospitalisation for infection before age 12 months: randomised controlled trial.

OBJECTIVE: To test for potential non-specific effects of an additional, early measles, mumps, and rubella (MMR) vaccine at age 5-7 months on risk of infection related hospitalisation before age 12 months. DESIGN: Randomised, double blinded, placebo controlled trial. SETTING: Denmark, a high income setting with low exposure to MMR. PARTICIPANTS: 6540 Danish infants aged 5 to 7 months. INTERVENTIONS: Infants were randomly allocated 1:1 to intramuscular injection with standard titre MMR vaccine (M-M-R VaxPro) or placebo (solvent only). MAIN OUTCOME MEASURES: Hospitalisations for infection, defined as all hospital contacts of infants referred from primary care for hospital evaluation and with an infection diagnosed, analysed as recurrent events, from randomisation to 12 months of age. In secondary analyses implications of censoring for date of subsequent diphtheria, tetanus, pertussis, polio, Haemophilus influenzae type B, and immunisation with pneumococci conjugate vaccine (DTaP-IPV-Hib+PCV), potential effect modification by sex, prematurity (<37 weeks' gestation), season, and age at randomisation were tested, and the secondary outcomes of hospitalisations ≥12 hours and antibiotic use were evaluated. RESULTS: 6536 infants were included in the intention-to-treat analysis. 3264 infants randomised to MMR vaccine experienced 786 hospitalisations for infection before age 12 months compared with 762 for the 3272 infants randomised to placebo. In the intention-to-treat analysis the rate of hospitalisations for infection did not differ between the MMR vaccine and placebo groups (hazard ratio 1.03, 95% confidence interval 0.91 to 1.18). For infants randomised to MMR vaccine compared with those randomised to placebo, the hazard ratio of hospitalisations for infection with a duration of at least 12 hours was 1.25 (0.88 to 1.77), and for prescriptions of antibiotics was 1.04 (0.88 to 1.23). No significant effect modifications were found by sex, prematurity, age at randomisation, or season. The estimate did not change when censoring at the date infants received DTaP-IPV-Hib+PCV after randomisation (1.02, 0.90 to 1.16). CONCLUSION: Findings of this trial conducted in Denmark, a high income setting, do not support the hypothesis that live attenuated MMR vaccine administered early to infants aged 5-7 months decreases the rate of hospitalisations for non-targeted infection before age 12 months. TRIAL REGISTRATION: EU Clinical Trials Registry EudraCT 2016-001901-18 and ClinicalTrials.gov NCT03780179.

Similar Skin Barrier Function in Persons with Type 1 Diabetes Compared with Healthy Controls.

Contact dermatitis because of use of diabetes devices is frequent in individuals with type 1 diabetes (TD1), especially in the pediatric age group, but the putative role of a constitutional impaired skin barrier in persons with TD1 is unclear. This study examined the skin barrier function by the measurement of natural moisturizing factor and free cytokines collected through skin tape strips, as well as biophysical markers and the skin microbiome, in persons with TD1 than to age- and sex-matched healthy controls. All measurements were done in nonlesional skin. We found that the skin barrier function was similar in children and adolescents with TD1 than to controls but found that the beta-diversity of skin microbiome at the buttock differed between the two groups. We conclude that individuals with TD1 have normal skin barrier function, and that the increased occurrence of contact dermatitis following pump and sensor use is explained by exogenous factors.