BACKGROUND:Heterogeneity in outcome reporting and inconsistent use of outcome measurement instruments in allergy and clinical immunology research affects the comparability, synthesis, and clinical applicability of study findings. Harmonisation efforts, particularly Core Outcome Set (COS) development, aim to address these challenges by establishing standardised, evidence-based and consensus-driven outcome recommendations. This systematic review aims to map available COS and other harmonisation processes (HP) in allergy and clinical immunology, evaluate their methodological approaches, and assess their alignment with established development standards. METHODS:We systematically searched MEDLINE, EMBASE, and the COMET Initiative database until June 7, 2024 to identify COS and HP. We included studies if they provided recommendations on 'core' outcomes and/or outcome measurement instruments. Data extraction included disease focus, methodological approach, stakeholder involvement, and adherence to the Core Outcome Set-STAndards for Development criteria. We synthesised the data at the initiative (process) level rather than the publication level because harmonisation initiatives are frequently iterative and reported across multiple papers (e.g., protocol, Delphi rounds, consensus statement, and subsequent instrument-selection outputs). RESULTS:A total of 15,612 records were identified, with 44 studies (representing 22 initiatives both finished and in development) meeting inclusion criteria. The majority of initiatives focused on asthma (n = 9), followed by eczema (atopic dermatitis n = 2; hand eczema = 1; eczema = 1), urticaria (n = 2), allergic rhinitis (n = 2), chronic rhinosinusitis (n = 1), celiac disease (n = 1), Immunoglobulin E (IgE)-mediated food allergy (n = 1), eosinophilic esophagitis (n = 1), and hereditary angioedema (n = 1). No COS or HP addressed drug allergy, anaphylaxis, or other immune-mediated allergic conditions. 'Quality of life' was consistently included in all COS with 'signs and symptoms', 'exacerbations' and 'disease control' frequently selected as well. Methodological approaches to COS development varied widely, with most employing Delphi surveys, consensus meetings, and stakeholder involvement, though levels of engagement differed. COS developers inconsistently adhered to Core Outcome Set-STAndards for Development criteria, with some initiatives demonstrating rigorous methodology while others lacked transparency in key developmental steps. CONCLUSION:This review highlights growing efforts to harmonise outcome assessment in allergy and clinical immunology. Major gaps remain in coverage and methodological rigour. Quality of life and patient-reported symptoms are frequently recommended outcomes, yet definitions and measurement tools are inconsistent. Strengthening methodological consistency and expanding COS development to neglected areas are critical next steps to improve outcome reliability and comparability in the field.

Background Dioxin and per- and polyfluoroalkyl substances (PFAS) exposure in fetal life and early infancy may be harmful for the male reproductive system. Objectives We investigated the associations between pre- and postnatal dioxin/PFAS exposure and semen quality in young adulthood. Methods The Ulm Birth Cohort Study is a population-based longitudinal birth cohort study (recruited 11/2000-11/2001). Maternal serum was collected shortly after delivery (mostly taken within the first two days) and maternal milk 6 weeks postpartum, immediately aliquoted, and stored at -80 ⁰C. Concentrations of dioxins (PCDDs, PCFDs and dioxin-like PCBs) were analyzed in milk in the year 2022 and PFAS in maternal serum in the year 2023. Semen provided by male offspring in 2021/22 was analyzed according to the 2010 WHO manual. Multivariable linear regression models were used to analyze the associations of (1) maternal dioxin/PFAS concentrations and of (2) cumulative dioxin/PFAS exposure with semen quality. Results Semen was available for n=98 males (age 20.4 ± 0.4 years; 86% were breastfed at 6 weeks). Median WHO2005-PCDD/F+PCB-TEQ concentration was 0.516 pg/g milk (n=77, IQR 0.296-0.715), median serum PFAS level (EFSA sum) was 10.8 µg/L (n=92, IQR 8.3-13.8). In adjusted analyses, we found no associations between concentrations of dioxin on a continuous scale with various measures of semen quality. For the continuous analysis of PFAS, a positive association with sperm concentration was seen in the partly adjusted cumulative exposure model, which was, however, not present after full adjustment. The mutual adjustment for dioxins and PFAS in statistical analysis revealed a significant negative association between dioxin levels in milk with sperm concentration and %-progressive motility and a significant positive association between PFAS levels in postpartum serum and sperm concentration. Conclusion While our data do not suggest an adverse association between early PFAS exposure and semen quality in adulthood, an adverse association with early dioxin exposure cannot be excluded. The small sample size and potential sources of bias or confounding call for cautious interpretation.

BACKGROUND:The inverse association of farm exposure with asthma and atopic conditions has been attributed to the diversity of environmental bacteria and fungi, but the specific taxa and the underlying mechanisms remain elusive. METHODS:We performed sequencing of the bacterial 16S ribosomal ribonucleic acid (16S rRNA) gene in mattress dust samples from 1018 schoolchildren from two German populations of the cross-sectional GABRIELA (Multidisciplinary Study to Identify the Genetic and Environmental Causes of Asthma in the European Community [GABRIEL] Advanced Study) survey. Bacterial metabolic pathways and enzymes were assessed bioinformatically, and metabolites were measured by using mass spectrometry. Statistical methods included network, interaction, and mediation analyses. RESULTS:Within the highly diverse microbial exposure in a farm environment, the study identified nine gram-positive environmental bacterial genera, whose composite score explained two thirds of the inverse association of farm exposure and asthma in a mediation analysis. The effect was independent of gram-negative farm-associated bacteria. A PICRUSt2 (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) analysis revealed nine pathways, whose enzymes were encoded by the identified genera and whose metabolites were detected in cowshed dust by using mass spectrometry. The metabolites included ligands of the human aryl hydrocarbon receptor (kynurenine and xanthine) and the peroxisome proliferator-activated receptor-γ (α-linoleic and stearidonic acid). Single nucleotide polymorphisms of the corresponding human receptor genes interacted with the composite score of the bacterial genera for asthma. Fungi and bacteriophages co-occurred with the beneficial bacteria but did not carry the protective effect. All results were replicated in independent populations. CONCLUSIONS:In this analysis, the inverse association of childhood asthma and farm exposure was largely mediated by exposure to gram-positive bacterial genera. Gene-environment interactions of a compound score of these bacteria with human receptors recognizing bacterial metabolites suggest novel approaches to asthma prevention.

INTRODUCTION:We investigated whether having more birch trees or more allergenic trees around home in early adolescence was related to worse lung function up to early adulthood in the German cities of Munich and Dresden. METHODS:The analytic sample included 1539 participants from the population-based ISAAC II/SOLAR II study who were aged 9-11 at baseline and 19-24 at follow-up. Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1/FVC were measured by spirometry at both time points. The number of birch trees, allergenic trees, and total trees, along with tree cover density and the normalized difference vegetation index (NDVI) were calculated in 300 m buffers around home at baseline. The associations were assessed by generalized least squares regressions with a variance-covariance structure accounting for heteroscedasticity and within-subject correlations. RESULTS:Participants living close to birch trees around age 10 tended to have slightly lower FEV1 and FVC up to early adulthood. These associations were not restricted to participants with asthma or hay fever. Similar, though much attenuated, associations were found for allergenic trees. No associations were found for the other exposures of interest. We saw some effect modification by ozone, nitrogen dioxide (NO2), and study town, but only for associations of NDVI with FEV1. DISCUSSION:Birch trees around the childhood home, as proxy of long-term exposure to allergenic birch pollen, were associated with slightly lower lung function up to early adulthood. Future studies on health effects of greenspace exposure should include species of plants.

Unvetted scientific claims about vaccines can spread rapidly and undermine decades of progress in immunization and public trust. A recent non-peer-reviewed analysis, promoted at political hearings, in the documentary "An Inconvenient Study," and on social media, has been used to suggest that vaccinated children experience higher rates of chronic illness than unvaccinated peers. Despite standard regression models, critical flaws - uncontrolled confounding, exposure misclassification, unequal follow-up, and outcome multiplicity, invalidate causal inference. An independent group of international experts critically appraises this analysis and contrast its claims with the consistent evidence confirming vaccine safety and effectiveness. We also show how poorly designed studies can distort public discourse, amplify misinformation, and fuel vaccine hesitancy. We outline actions to strengthen research integrity, such as transparent data sharing, labeling of non-peer-reviewed content, and evidence-based communication. Safeguarding public health demands that vaccine evidence be methodologically sound, reviewed, and interpreted by qualified experts.

Adequate sleep is essential for child and adolescent development, driving extensive research across scientific disciplines. This umbrella review provides a comprehensive overview of existing evidence on media consumption and sleep and thereby lays the foundation for identifying key concepts and gaps. An inclusive systematic search for reviews reporting literature searches was conducted in 02/2021 and updated last in 09/2024. Methodological quality of the included reviews was assessed using AMSTAR-2. We included 84 reviews reporting on the association between media use and sleep in individuals aged 0-18 years. The field is dominated by reviews of low methodological quality, mainly including original cross-sectional studies with subjective measures in older children and adolescents. A total of 475 original articles were covered by the reviews; only 10 of them appeared in at least seven and at most nine reviews. Screen time generally had a negative impact on sleep, though evidence varied from very low to strong. Evidence for effects of conventional books on sleep remains inconclusive. High quality systematic reviews are needed to evaluate robust studies using objective measures of sleep and contemporary media use across all age groups up to adolescence and to explore the impact of non-digital media use on sleep, considering age and gender differences.

IntroductionHuman milk oligosaccharides (HMOs) are bioactive components of breast milk that play a key role in shaping infant immune development and susceptibility to infections. This study investigated associations between 71 known and novel HMOs measured at 6 weeks and 6 months postpartum with infant infections during the first 2 years of life.MethodsA total of 73 HMOs were analyzed in human milk sampled at 6 weeks (n = 144) and 6 months (n = 133) using LC-ESI-IM-qTOF-MS. Infections in infants were assessed using physician-reported questionnaires at 1 and 2 years. Modified Poisson regression was used to assess associations, adjusted for relevant covariates and corrected for multiple testing (FDR < 0.010).ResultsHigher levels of fucosyl(1-3)-iso-lacto-N-octaose, lacto-N-tetraose (LNT), and sialyllacto-N-tetraose b (LSTb) at 6 weeks were associated with higher likelihood of lower respiratory tract infection (LRTI) at 1 year of age. In contrast, elevated difucosyldisialyllacto-N-hexaose-X2 and difucosyl-lacto-N-hexaose II in non-secretor milk were linked to reduced likelihood of otitis media (OM) in the cumulative 2-year period. Higher levels of LNT2 and LSTa in secretor milk at 6 months were associated with a higher likelihood of LRTI in the first and cumulatively up to the second year of life, respectively.ConclusionThese findings suggest that specific HMOs may influence early-life infection susceptibility. However, the associations likely reflect a complex, dynamic balance in human milk composition, potentially driven by early microbial exposures or maternal responses. Further research is needed to clarify whether HMOs directly modulate susceptibility to infection or act through broader immunological pathways.

This scoping review explores the regional distribution and scope of human milk research in Africa. Given the nutritional and immunological importance of human milk, understanding regional research activity is crucial for addressing maternal and infant health challenges across the continent. A systematic search of the Web of Science database was conducted up to 10/2023 adhering to PRISMA-ScR guidelines. All relevant publications on human milk research in Africa were included, regardless of type or quality. Studies were categorized based on key characteristics including study design, geographic location, and focus areas. A total of 459 reports on human milk sampling were identified, published between 1952 and 2023, with 81% full text available. Research activity was concentrated in Southern, Eastern, and Western Africa, with South Africa, Kenya, and Nigeria leading in HIV, micronutrient, and immunological research. Descriptive studies accounted for 34% of publications. HIV-related research (21.6%) predominated in regions with high HIV prevalence. There was notable underrepresentation from Northern and Central Africa, with countries like Niger and Gabon showing limited activity. Micronutrient and pesticide research prevailed in South Africa, Kenya, and Nigeria, while human milk microbiota research was concentrated in South Africa and Kenya. This scoping review reveals significant regional disparities in human milk research across Africa. Southern and Eastern Africa lead in key areas, but Northern and Central Africa remain underrepresented. To address these gaps, increased collaboration, funding, and region-specific research are essential. Expanding research efforts will enhance understanding and improve breastfeeding practices and infant health across the continent.

Background:While cross-ancestral differences in glucose and lipid metabolism are widely reported in adults, there is a paucity of data on pregnant women during various stages of pregnancy. There is no consensus on what defines normal lipid ranges during pregnancy. Establishing reference ranges is crucial to reduce the risk of missing associated maternal and fetal health issues. Therefore, we aimed to investigate the metabolic profiles of healthy pregnant women and to establish national Rwandan reference ranges for these metabolites. Methods:We derived the data from two ongoing longitudinal cohort studies conducted in predominantly rural Rwanda and urban Germany (Leipzig), providing repeat data from the second and third trimesters of pregnancy. We measured concentrations of glucose, total cholesterol (TC), high-density lipoprotein cholesterol (HDL), and triglycerides (TG), and estimated their associations with trimesters and cohorts using multivariable linear regression. We estimated the reference ranges using the 5th and 95th percentiles for each metabolic marker. Results:For Rwanda and Leipzig, lipids and lipoproteins increased across trimesters, except for HDL, which remained equally low for Rwanda and significantly decreased for Leipzig. Concentrations of TC, low-density lipoprotein, and non-HDL were significantly higher in Leipzig compared to Rwanda for both trimesters, while HDL was significantly lower in Rwanda. Rwanda exhibited significantly higher TG levels in the second trimester than Leipzig, although this difference did not persist into the third trimester. Glucose concentrations were significantly higher in Rwanda than in Leipzig for both trimesters. Conclusions:This is the first representative study investigating lipid and lipoprotein concentrations in pregnant women from Rwanda and comparing them to a European sample. This study shows that lipid, lipoprotein, and glucose concentrations differ by ancestry and stage of pregnancy. The higher TG and glucose concentrations in Rwanda may indicate an emerging burden of metabolic disorders in Africa.

The long-tern implications of stress during university for individuals’ mental health are not well understood so far. Hence, we aimed to examine the potential effect of stress while studying at university on depression in later life. We analysed data from two waves of the longitudinal Study on Occupational Allergy Risks. Using the ‘work overload’ and ‘proving oneself’ scales of the Trier Inventory for Chronic Stress and the Patient Health Questionnaire-2 (PHQ-2), participants reported chronic stress during university (2007–2009, mean age 22.2 years, T1) and depressive symptoms ten years later (2017–2018, mean age 31.6 years, T2). We performed linear regression analyses to explore the association between stress during university (T1) and later depressive symptoms (T2). Participants (N = 548, 59% female) indicated rather low levels of stress and depression (PHQ-2 mean score: 1.14 (range: 0–6)). We observed evidence for a linear association between overload at T1 and depression at T2 (regression coefficient (B) = 0.270; 95% confidence interval (CI) = 0.131 to 0.409; standardised regression coefficient (β) = 0.170). Our analyses yielded evidence for an association between chronic stress while studying and risk of depressive symptoms later in life. This finding underlines the importance of implementing sustainable preventive measures against stress among students.

Objectives:To assess potential associations between maternal employment after childbirth with subsequent child mental health problems. Methods:We analyzed 536 families of a prospective birth cohort to estimate trajectory classes of maternal employment 0-36 months postpartum. Multivariable linear regression models were employed to examine associations between (1) trajectory classes and (2) maternal employment status at 12 months postpartum with child mental health problems at 4, 5, and 6 years of age. Results:We identified five different trajectory classes of maternal employment after childbirth. For boys, trajectory classes 2 and 3 (characterized by relatively high maternal working hours/week) were associated with more mental health problems at ages 5 and 6 compared to class 1 (relatively low or no working hours/week). No associations were found for classes 4 (part-time after 2 years) and 5 (increasing and subsequently decreasing working hours/week) among boys. For girls, class 5 was associated with less mental health problems at ages 5, and 6 compared to class 1. Analysis of maternal employment status at 12 months postpartum showed less mental health problems for part-time employment at 12 months postpartum compared to no-employment among boys. Conclusion:Mixed results were found for maternal employment after childbirth and boys' mental health depending on the measure used. No detrimental associations were found for girls.

Preschool health examination is one of the main tasks of the German public health service. The social-paediatric screening used in this process is SOPESS, the validated tool for assessing the developmental status of preschool children. The results enable tracking of developmental abnormalities across regions and over time, as well as deriving individual and preventive action requirements. In practice, however, the data show relevant method-related heterogeneity across teams and public health services that cannot be explained solely by differences in the study population. This affects the data validity and their optimal use for regional prevention planning and health reporting.The KOMET-SEU project aimed, on the one hand, to assess and illustrate method-related heterogeneity and its causes, and to develp and evaluate an online training program, on the other, to strengthen public health service in its implementation and documentation of SOPESS, to reduce the data's heterogeneity and to support data usage.The project was based on the Public Health Action Cycle and used a logical model as a theoretical basis. To develop and evaluate the online training, quantitative and qualitative methods were combined. The objectives were achieved in four work packages (WP): WP 1 established the statistical basis for assessing and depiction of method-related heterogeneity. WP 2 used surveys done with employees of the public health services to examine the causes of heterogeneity and relevant contextual factors for data collection. In WP 3, that information was used to construct and test an online training program. WP 4 implemented that training in several public health services and evaluated its processes and effects. Detailed results of the WP can be found in this issue of "Das Gesundheitswesen".The mixed-methods approach and participatory intervention development should help strengthen the skills of the employees of public health services in using the SOPESS and expand examinational competences within the teams. Thus, the KOMET-SEU project could make an important contribution to supporting the public health service in the use of SOPESS data. Whether it will be possible to reduce the heterogeneity in the SOPESS data itself must be investigated further. The ground-work has been laid.

Introduction:The COVID-19 pandemic and associated preventive measures influenced family health and behavior, leading to diverse effects on sleep. Methods:This study examined sleep characteristics before, during and after the COVID-19 pandemic in children (n = 558), mothers (n = 465), and fathers (n = 318) in Germany, using data from the prospective Ulm SPATZ Health Study. We compared the period from April 2017 to May 2023 (children aged 5-10 years) with the period from 15 March 2020 to 3 April 2022, defined as "COVID-19 pandemic." Sleep quality was measured using the Children's Sleep Habits Questionnaire (CSHQ) and the Pittsburgh Sleep Quality Index (PSQI), among children and parents, respectively. Multivariable mixed models were used to assess the associations of the COVID-19 pandemic compared to before and after the pandemic with sleep characteristics among boys, girls, mothers, and fathers, separately. Results:Child and parent sleep quality showed a weak correlation among 6-year-old boys and their mothers. A moderate correlation was observed between mothers' mental health and boys' sleep quality at ages 5, 6, and 9. Parents' mental health showed a moderate correlation with their sleep quality. Multivariable mixed models revealed better sleep quality (lower CSHQ total scores) among boys during the COVID-19 pandemic compared to before and after. Daytime sleepiness decreased among boys and girls, while no significant changes were found for sleep duration and sleep latency. Among mothers, sleep duration increased on free-days, while fathers experienced increased sleep duration on work-days, along with increased sleep efficiency. Discussion:This study showed that family sleep quality (indexed with the CSHQ and PSQI) did not decrease during the COVID-19 pandemic compared to sleep quality measured at one (parents) or two (children) annual time points before the pandemic and up to one after it. Instead, parental sleep duration increased, children experienced reduced daytime sleepiness, and boys exhibited improved sleep quality. To effectively optimize public health during a pandemic, findings on sleep quality should be interpreted in conjunction with findings on mental health, given their interrelated nature, as also indicated by our study.

The influence of maternal secretor status and child fucosyltransferase (FUT2) polymorphisms on respiratory and ear infections, and growth, is an emerging research area. But, the impact of discordant secretor status between mother and infant, where their secretor status differs, remains underexplored. This study investigated how infant FUT2 single nucleotide polymorphisms (SNPs) modify the association between maternal secretor/non-secretor milk phenotypes and child outcomes such as infections, and growth during the first two years of life in discordant mother-infant pairs. Data from n = 539 mother-infant pairs in the Ulm SPATZ Health Study (SPATZ) and n = 488 pairs in the Ulm Birth Cohort Study (UBCS) were analysed using logistic, modified Poisson, and linear regression models. A significant proportion of infants in both cohorts were heterozygous secretors (46% in SPATZ and 45% in UBCS), and about a third had discordant secretor status with their mothers. Non-secretor infants receiving secretor milk in SPATZ showed a significant increase in BMI between week 4/5 and month 3/4 compared to secretor infants. But these associations were not significant after adjusting for confounders and correcting for multiple testing (α threshold = 0.0035). Despite the non-significant results, the findings emphasize the need for further research on discordant secretor status and its health implications.

Früherkennungsuntersuchungen wie die Kita-Untersuchung (KU) im 4. Lebensjahr sind bedeutsam, um etwaige Förderbedarfe vor Schuleintritt frühzeitig zu erkennen und Fördermaßnahmen einzuleiten. Die Umsetzung der KU erfolgt in Deutschland unter Beteiligung der Gesundheitsämter, variiert jedoch stark zwischen den Bundesländern. Am Beispiel des Bundeslands Sachsen zielt die Studie darauf ab, die Perspektive von Ärztinnen und Ärzten des Kinder- und Jugendärztlichen Dienstes (KJÄD) auf die KU zu erfassen im Hinblick auf: (1) die Eignung zur Erfassung von Förderbedarfen und die Inanspruchnahme, (2) die Durchführungs- und Umgebungsfaktoren sowie (3) die Auswirkungen der COVID-19-Pandemie („coronavirus disease 2019“). Die Studie basiert auf einem quantitativen, querschnittlichen Untersuchungsdesign. Mithilfe eines Online-Fragebogens wurden N = 56 Ärztinnen und Ärzten des KJÄD befragt. Die KU wurde durchweg als sinnvolles Untersuchungsangebot eingeschätzt (82

BACKGROUND:Atopic dermatitis (AD) is a common allergic skin disease. We aimed to assess the secular changes in the cumulative incidence of childhood AD and its risk factors over a decade. METHODS:We used data from two methodologically similar cohort studies in Ulm, Germany, the Ulm Birth Cohort Study (UBCS, recruited in 2000/2001) and the Ulm SPATZ Health Study (recruited in 2012/2013). The cumulative incidences of AD as reported by their family physicians and parents up to the age of 4 years were compared by log-rank test across the two cohorts, using propensity score-based weighting to control confounders. We fitted multivariable Cox regression models to estimate hazard ratios and 95% confidence intervals (CIs) for the factors associated with the occurrence of physician- and parent-reported AD and compared the results between the two cohorts. RESULTS:The 4-year cumulative incidence (95% confidence interval) of physician-reported AD (27.4% (24.4%-30.5%) in UBCS [2000/2001] vs. 26.4% (22.8%-30.2%) in SPATZ [2012/2013], p = 0.728) and parent-reported AD (14.5% (12.2%-17.0%) in UBCS [2000/2001] vs. 16.7% (14.0%-19.7%) in SPATZ [2012/2013], p = 0.211) remained stable between the two cohorts after propensity score-based weighting. We observed the changes in the association between AD and certain risk factors (e.g., family history of AD and infantile antibiotic use) over the decade, but the results need to be interpreted with caution due to the limited sample size, relatively high attrition rate and demographic differences between the two cohorts. CONCLUSIONS:Over the decade, childhood AD incidence remained stable. Further studies are needed to verify whether there is a growing importance of environmental and microbiota-related factors for AD development over time.