Effect of mothers' health literacy on early childhood allergy prevention behaviours: results from the KUNO-Kids health study.

BACKGROUND: Parents can engage in several behaviours with regard to early childhood allergy prevention (ECAP). These can be related to diet of mother/child and the modification of the home environment; not all of them are justified by current evidence. Previous studies showed that parental health literacy (HL) is related to favourable health behaviours directed at the child. This study aimed to investigate the causal effect of mothers' HL on ECAP behaviours and to test different moderators of this effect. METHODS: One thousand six hundred sixty-two mothers participating in the KUNO-Kids health study in the area of Regensburg, Germany were surveyed on HL (assessed via the health care scale of the Health Literacy Survey-EU questionnaire, HLS-EU-Q47) and ECAP behaviours implemented during pregnancy and the child's first year of life. Patterns in ECAP behaviours were identified by latent class analysis. Multinomial regression modelling was performed with HL as exposure, ECAP as outcome variable, allergy risk, parental competence and bonding, anxiety and depression as moderators as well as potentially confounding variables. RESULTS: We identified three classes of ECAP behaviours (class 1: "breastfeeding " N = 871; class 2: "allergen-avoidance " N = 490; class 3: "mixed behaviours " N = 301). In univariable as well as fully adjusted regression models, compared to class 1, class 2 was negatively, and class 3 was not associated with HL. None of the tested moderating variables altered the association between HL and ECAP significantly. CONCLUSIONS: We found an effect of mothers' HL on ECAP behaviours: lower HL of mothers increased allergen-avoiding behaviour directed at their child, while decreasing the chance of exclusive breastfeeding. Improving HL could contribute to the implementation of recommended ECAP behaviours in families, especially to the reduction of allergen-avoiding behaviours.

Association of umbilical cord serum TARC/CCL17 with childhood allergies: A birth cohort study.

BACKGROUND: Early identification of infants at high risk of allergies can improve the efficacy of preventive interventions. However, an established quantifiable risk assessment method in the early postnatal period does not exist. TARC (or CCL17) is a Th2 chemokine used as an activity marker for atopic dermatitis (AD). Therefore, we evaluated the association between cord blood TARC (cTARC) and the development of allergic diseases in childhood. METHODS: This is a high-risk birth cohort for allergy, consisting of children with a family history of allergy. We collected 263 pairs of maternal and child cord blood samples perinatally and child blood samples at ages 1, 2, and 5 years. TARC and allergen-specific immunoglobulin E levels were measured, and the relationship between allergic diseases was analyzed. RESULTS: The median cTARC was 989 pg/mL (interquartile range [IQR]: 667-1430 pg/mL). The cTARC levels in children who developed AD were higher than those in children who did not develop AD, and the association strengthened with younger age (median [IQR] at 1 year: 1285 [816-1965] vs. 933 [662-1330] pg/mL, p < 0.01; at 2 years: 1114 [787-1753] vs. 950 [660-1373] pg/mL, p = 0.02). In the multivariate analysis, cTARC was associated with AD, egg white sensitization, food allergy, allergic rhinitis, and Japanese cedar pollen sensitization. CONCLUSIONS: cTARC was associated with the development of allergic diseases and allergen sensitization in early childhood. These results suggest that, infantile AD-mediated atopic march starts during fetal life, and this immune status is reflected in the cTARC at birth.

Quality of life against seasonal vs perennial allergens: ESPRINT-15 modified in the pediatric population.

INTRODUCTION: Allergic rhinitis (AR) is a clinical syndrome characterized by IgE-mediated inflammation of the nasal mucosa. The present study investigates the quality of life (QoL) with AR among adults, using widely validated questionnaires, unlike in pediatric patients. MATERIALS AND METHODS: A cross-sectional descriptive observational study was conducted, analyzing the QoL of 102 children with AR aged between 10-15 years, belonging to two health centers (HC) in Zaragoza and two HC in Coruña. The comparison of means between the two groups is carried out using the Student's test or the Mann-Whitney test, considering a value of p˂0.05 to be significant. RESULTS: Around 102 children were studied, with a majority (59.8%) being male and a mean age of 12 years. Around 76.5% have a family history of atopy. It was found that AR is more prevalent in Zaragoza (p ˂0.005), and asthmais highly prevalent in Coruña (p ˂0.001). The most important sensitizations are pollen in Zaragoza (p ˂0.05) and dust mites in A Coruña (p ˂0.001). More treatment needs and associated comorbidities (p˂0.05) were observed in A Coruña. The results of the ESPRINT-15 show that 63% of the patients have a good QoL, 27% fair, and 8.8%, poor. Those sensitized to mites have a worse score (p = 0.02). It was found that 52% of children experienced improvement during home confinement, with no notable differences between the two populations. The use of the mask favored QoL in patients from Zaragoza (p ˂0.001). CONCLUSION: It was concluded that AR influences the QoL in pediatric patients. Greater QoL involvement, need for treatment, and comorbidities are observed in patients sensitized to dust mites compared to those sensitized to pollens. It was also observed that masks improved the symptoms, stopping patients being sensitized to pollens.

Childhood asthma: Novel endotyping by cytokines, validated through sensitization profiles and clinical characteristics.

BACKGROUND: Specific allergy sensitization pattern, using "component-resolved diagnosis" (CRD), is a central component of allergy and asthma in childhood. Besides this, allergic asthma has been characterized by a Th2-shifted endotype with elevation of classical Th2 cytokines. Recently, other endotypes with distinct mechanisms focusing on cytokine regulation evolved, yet those pathways are still not well understood. OBJECTIVE: (a) To define reproducible immunological endotypes using cytokine expression in an asthma cohort and (b) to characterize their sensitization profile and clinical phenotype. METHODS: Supernatants from PBMCs of 234 children (median age 10 years) of an asthma cohort were analysed for cytokine expressions. The children were split into a training (n = 49) and validation (n = 185) group. The training group was used to identify immunological endotypes by clustering cytokine expressions, which were then assessed regarding clinical characteristics and specific IgE of recombinant allergen components. Next, our findings were validated in the validation group. RESULTS: We identified novel endotypes based on primarily unstimulated cytokine expression. One endotype showed an IFN-γ/Interleukin (IL)-17/IL-5 predominance, a different sensitization pattern (high in birch/apple; p < .01), and inferior lung function (p < .01). A second endotype grouped young children with food allergy and reduced lung function. Our findings were reproducible in the validation group. CONCLUSION AND CLINICAL RELEVANCE: We identified two novel clinical asthma endotypes via cytokine expression pattern with distinct sensitization patterns. These novel findings are critical for clinical guidance and open avenues for identifying underlying mechanisms and more patient-specific therapies.

Investigation of Quality of Life Determinants in Children with Food Allergies.

BACKGROUND: Food allergy (FA) in children impacts their own and their family quality of life (QoL). The association of specific FA factors with the various domains of health-related QoL (HRQL) in children is unclear. OBJECTIVE: The aim of this study was to evaluate FA characteristics in primary school children as determinants of components of HRQL. METHODS: Children with FA were recruited from the allergy clinic of a tertiary children's hospital. Demographic and clinical data were retrieved from their records, and 3 HRQL questionnaires were administered: the FA QoL Questionnaire-Child Form (FAQLQ-CF), the FA independent measure (FAIM), and the Pediatric QoL Questionnaire (PedsQL™). Stepwise multiple linear regression analysis was carried out to investigate the correlation between FA characteristics and the scores on the HRQL scales. Bonferroni correction for multiple comparisons was set at p < 0.0002. RESULTS: Of 172 primary schoolchildren with FA invited to take part, 110 participated (response rate 64%), of whom 83 (75.5%) were male, aged 7.5-12.3 years (mean 10.0 ± 1.4) years. From 38 demographic and clinical characteristics, 10 were excluded on initial data analysis and 28 proceeded to bivariate analysis with the scores on FAQLQ-CF, FAIM, PedsQL™, and their subscales. Most of the 28 showed no correlation with the scores; only 4 were entered into multivariate analysis with FAQLQ-CF and PedsQL™ scores, none of which, finally showed significant association. CONCLUSION: The HRQL of children with FA did not depend on gender, age, number, and type of allergen or the characteristics of the most severe allergic reaction.

Exposure to perfluoroalkyl substances and allergic outcomes in children: A systematic review and meta-analysis.

BACKGROUND: Perfluoroalkyl substances (PFASs) are persistent organic pollutants and widespread throughout the environment. Although exposure to PFASs may contribute to the development of allergic diseases in children, evidence about this association remains inconclusive. OBJECTIVE: To conduct a systematic review and meta-analysis to assess the association between PFASs exposure and allergic diseases in children based on current evidence. METHODS: The databases including PubMed, EMBASE, and Web of Science were searched to identify all observational studies that examined the association between PFASs exposure and the risk of childhood allergic diseases. The Newcastle-Ottawa Scale was used to evaluate the quality of case-crossover studies, and a previously validated quality assessment framework was used for observational studies lacking control groups. Random-effects meta-analysis models were applied to pool odds ratio (OR) with 95% confidence intervals (CIs). RESULTS: From an initial 94 articles (after duplicate removal), 13 studies through full-text assessment were included for quantitative assessment and descriptive synthesis. They are ten cohort studies, two cross-sectional studies, and one case-control study. The pooled estimates showed that perfluorononanoic acid (PFNA) was associated with eczema (OR = 0.89, 95% CI = 0.80-0.99), perfluorooctanesulfonic acid (PFOS) with atopic dermatitis (OR = 1.26, 95% CI = 1.01-1.58), and perfluorooctanoic acid (PFOA) with allergic rhinitis (OR = 1.33, 95% CI = 1.13-1.56). However, no such significant associations were found for wheeze and asthma. CONCLUSIONS: The meta-analysis results suggest that PFASs exposure could potentially be associated with eczema, atopic dermatitis, and allergic rhinitis during childhood, but not with childhood asthma or wheeze. Future studies are needed to verify these findings.

Prenatal exposure to bisphenol - A is associated with dysregulated perinatal innate cytokine response and elevated cord IgE level: A population-based birth cohort study.

BACKGROUND: Reports on the relationship between prenatal exposure to bisphenol-A (BPA) and the development of childhood allergy have been conflicting. This study aimed to investigate the impact of prenatal BPA exposure on several objective outcomes such as cytokine profile, atopic sensitization, and infant lung function (ILF) tests in addition to clinical allergic symptoms. METHODS: A subset of 274 children from the PATCH cohort study with available cord BPA data were followed until 3 years of age. Total and specific IgE level and Toll-like receptor (TLR) stimulated cytokine production were assessed yearly since birth. ILF such as tidal volume, VmaxFRC, airway resistance and compliance were performed at least once before the age of 2 years. Allergic outcome was determined by questionnaires and physician's assessment. RESULTS: There was significant association between BPA concentration and IgE level in the cord blood (p < 0.01), but the correlation was no longer significant at ages 1 through 3 years. In addition, cord BPA concentration was associated with dysregulated TLR stimulated TNF-α and IL-6 production, but the correlation was significant only at birth. No relationship was found between cord BPA concentration and ILF measurements or allergic symptoms (wheezing, rhino-conjunctivitis, or eczema) throughout early childhood. CONCLUSION: Results showed that prenatal exposure to BPA was not associated with increased risk of childhood allergy or impaired ILF. However, with its impact on biomarkers for allergy such as alterations in perinatal cytokine profile and elevated cord IgE level, the potential role of prenatal BPA exposure on the development of allergy cannot be disregarded.

Prenatal Diet and the Development of Childhood Allergic Diseases: Food for Thought.

PURPOSE OF REVIEW: The development of allergic disease is shaped by genetics and the environment, including diet. Many studies suggest a role for maternal diet during pregnancy. In this article, we discuss potential mechanisms by which specific nutrients, particular foods, and dietary patterns may influence allergic disease development and review studies examining the relationship between prenatal diet and the risk of childhood allergy. RECENT FINDINGS: The combination of in utero exposures and genetic predisposition may contribute to the development of allergic disease by altering immune and organ development. Inflammation predominates in the first and third trimesters whereas the second trimester is characterized by anti-inflammatory and Th2 immune responses. Maternal dietary exposures during pregnancy may interact with inherited genetic risk factors influence immune system development. There are varied results regarding the impact of maternal prenatal diet on the development of childhood allergies. Well-designed randomized controlled studies are needed to clarify this area.

The use of the MeDALL-chip to assess IgE sensitization: a new diagnostic tool for allergic disease?

BACKGROUND: Allergic sensitization is frequently present in asthma and rhinitis, but the role of specific immunoglobulin E (s-IgE) is not always clear. Multiple s-IgE analyses may provide insight into this relationship, thus a microarray chip was developed within the EU-funded MeDALL project. The main objective was to evaluate the performance of the MeDALL-chip compared to ImmunoCAP and skin prick test (SPT) in detecting allergic sensitization in children and secondarily to investigate the association to asthma and allergic rhinitis. METHODS: From the 'Environment and Childhood Asthma Study', 265 children were investigated at 10 and 16 yr of age with clinical examination, interview, SPT, ImmunoCAP, and the MeDALL-chip including 152 allergen components in the analysis. RESULTS: Allergic sensitization at 10 yr was more frequently detected using the MeDALL-chip (38.1%) compared to the ImmunoCAP (32.8%) (p = 0.034) and SPT (25.5%) (p < 0.001), but no significant difference was seen at 16 yr (MeDALL-chip 49.8%, ImmunoCAP 48.6%, SPT 45.8%). The MeDALL-chip did not differ significantly from the ImmunoCAP or SPT in terms of detecting allergic sensitization in subjects with rhinitis or asthma at 10 or 16 yr. CONCLUSION: The prevalence of allergic sensitization increased by all three diagnostic tests from 10 to 16 yr was similar by SPT and ImmunoCAP and significantly higher with the MeDALL-chip at 10 yr. All three tests were comparable for identification of allergic sensitization among children with current rhinitis or asthma.

Validation of a Comprehensive Early Childhood Allergy Questionnaire.

BACKGROUND: Parental questionnaires to assess incidence of pediatric allergic disease have been validated for use in school-aged children. Currently, there is no validated questionnaire-based assessment of food allergy, atopic dermatitis (AD), and asthma for infants and young children. METHODS: The Comprehensive Early Childhood Allergy Questionnaire was designed for detecting AD, asthma, and IgE-mediated food allergies in children aged 1-5 years. A nested case-control design was applied. Parents of 150 children attending pediatric outpatient clinics completed the questionnaire before being clinically assessed by a pediatrician for allergies. Sensitivity, specificity, and reproducibility of the questionnaire were assessed. RESULTS: Seventy-seven children were diagnosed with one or more current allergic diseases. The questionnaire demonstrated high overall sensitivity of 0.93 (95% CI 0.86-0.98) with a specificity of 0.79 (95% CI 0.68-0.88). Questionnaire reproducibility was good with a kappa agreement rate for symptom-related questions of 0.45-0.90. CONCLUSIONS: Comprehensive Early Childhood Allergy Questionnaire accurately and reliably reflects the presence of allergies in children aged 1-5 years. Its use is warranted as a tool for determining prevalence of allergies in this pediatric age group.

Evaluation of Childhood Allergy Risk Among Pregnant Women in a Tertiary Care Hospital in Thailand.

OBJECTIVES: This study aims to evaluate the prevalence of pregnant women whose children are at higher risk for childhood allergies and to assess knowledge of risk assessment and prevention strategies. METHODS: A cross-sectional study was conducted on 310 pregnant women in an antenatal care clinic at a tertiary care hospital in Thailand. In addition to baseline demographic and obstetric characteristics, all participating pregnant women were asked to complete a questionnaire regarding risk evaluation and knowledge of childhood allergies on various topics. A childhood allergy risk assessment was evaluated based on the history of allergy disease in immediate family members. The questionnaire on knowledge was derived from a guideline issued by the Allergy, Asthma, and Immunology Association of Thailand, with possible scores of 0-30. RESULTS: The mean maternal age was 30.6 years, and 139 (44.8%) were nulliparous. Overall, 86 couples (27.7%) were at high risk for childhood allergies. The mean total knowledge score was 15.2 out of 30, and only 24 women (7.7%) had an overall score of >20, and 40 women (12.9%) had an overall score of ≤10. The mean knowledge score for almost every subtopic was less than half of the possible points, except for the risk reduction strategies during pregnancy. Comparisons between those with higher and lower scores (≥16 vs. ≤15 points) showed that women with higher knowledge scores were significantly more likely to have had a previous child with an allergy (p=0.010). CONCLUSION: The prevalence of pregnant women whose children were at higher risk for childhood allergies was 27.7% (86 of 310 couples). The women had limited knowledge of childhood allergies with regard to risk assessment, risk reduction strategies, and various interventions. The only factor associated with a higher knowledge score was having a previous child with an allergy.

Research protocol and recruitment redesign of a study of pregnant women and their infants during the COVID-19 pandemic: Childhood Allergy and the NeOnatal Environment (CANOE).

Background: Recruitment for research studies is a challenging endeavor that was further complicated by the coronavirus disease 2019 pandemic. We launched a new multicenter birth cohort, Childhood Allergy and the NeOnatal Environment (CANOE), supported by the National Institutes of Health in January 2020 across 4 sites. Although the pandemic temporarily halted clinical research, we restructured the study and instituted novel recruitment methods that we hypothesized would enable brisk enrollment when research activities resumed. Objective: We sought to develop protocol modifications and recruitment methods that promote successful recruitment of diverse populations in clinical research despite a global pandemic. Methods: Even though study activities were suspended, we modified recruitment strategies to limit in-person contact, shifting toward alternative HIPAA-compliant methods such as clinician referrals, institutional social media, and telemedicine screening and consent procedures. Protocol changes included reducing the frequency of in-person visits, leveraging clinical care visits to collect biospecimens, expanded self-collection of samples at home, and making study materials available online. Results: Remote methods, including targeted social media posts, mailed letters, and email, combined with in-clinic recruitment with modifications for social distancing led to successful recruitment at all sites. Rates of consent have been similar across recruitment sites, with the highest rates of enrollment of mother-infant dyads realized by sites that implemented multiple recruitment strategies. Conclusions: Study procedures that prioritize health and safety measures such as social distancing, study participant convenience, and use diverse recruitment strategies enable successful enrollment of pregnant women and their newborns into clinical research while adhering to public health restrictions during a global pandemic.

Di(2-ethylhexyl) phthalate mediates IL-33 production via aryl hydrocarbon receptor and is associated with childhood allergy development.

Background: Few studies assess cord blood biomarkers to predict prenatal exposure to di(2-ethylhexyl) phthalate (DEHP) on the development of allergic diseases later in childhood. IL-33 has been indicated to play an important role in allergic diseases. We evaluated the association of prenatal DEHP exposure and IL-33 in cord blood on the development of allergic diseases. We also investigated the mechanism of DEHP in human lung epithelial cells and asthma animal models. Methods: 66 pregnant women were recruited, and their children followed when they were aged 3 years. Maternal urinary DEHP metabolites were determined using liquid chromatography-electrospray-ionization-tandem mass spectrometry. The effect of DEHP on IL-33 production was investigated in human lung epithelial cells and club cell-specific aryl hydrocarbon receptor (AhR) deficiency mice. ELISA and RT-PCR, respectively, measured the IL-33 cytokine concentration and mRNA expression. Results: The concentrations of maternal urinary DEHP metabolites and serum IL-33 in cord blood with childhood allergy were significantly higher than those in the non-childhood allergy group. DEHP and MEHP could induce IL-33 production and reverse by AhR antagonist and flavonoids in vitro. Enhanced ovalbumin-induced IL-4 and IL-33 production in bronchoalveolar lavage fluid (BALF) by DEHP exposure and suppressed in club cell-specific AhR null mice. Kaempferol has significantly reversed the DEHP effect in the asthma animal model. Conclusions: Cord blood IL-33 level was correlated to childhood allergy and associated with maternal DEHP exposure. IL-33 might be a potential target to assess the development of DEHP-related childhood allergic disease. Flavonoids might be the natural antidotes for DEHP.

Maternal antibiotic exposure and childhood allergies: The Japan Environment and Children's Study.

Background: The association of maternal antibiotic exposure during pregnancy with childhood allergic diseases remains unclear. Objective: We aimed to evaluate the association of maternal exposure to antibiotic use during pregnancy with childhood allergic diseases up to the age of 3 years by using data from a large Japanese birth cohort. Methods: We analyzed data on 78,678 pregnant women and their offspring aged 0 to 3 years. Prenatal antibiotic exposure was defined as the use of any antimicrobial agent during pregnancy. Information was collected from maternal interviews and medical record transcripts. The outcome variables in this study included preschool asthma, wheezing, food allergy, atopic dermatitis, eczema, allergic rhinoconjunctivitis, and any allergic disease. We used logistic regression analysis to evaluate the association of antibiotic exposure during pregnancy with childhood allergic diseases. Results: Among the participating mothers, 28.5% used antibiotics during pregnancy. Antibiotic exposure during pregnancy was associated with preschool asthma (adjusted odds ratio [aOR] = 1.12 [95% CI = 1.06-1.19]), wheezing (aOR = 1.11 [95% CI = 1.07-1.15]), allergic rhinoconjunctivitis (aOR = 1.10 [95% CI = 1.03-1.17]) and any allergic disease (aOR = 1.09 [95% CI = 1.05-1.14]) in offspring up to age 3 years. In contrast, maternal antibiotic use was not associated with food allergies, atopic dermatitis, or eczema. Additionally, the significant associations were not influenced by the timing of antibiotic exposure, sex of the infants, or maternal history of allergies. Conclusion: Maternal antibiotic exposure during pregnancy is associated with an increased risk of childhood respiratory allergies.

Childhood allergy susceptibility: The role of the immune system development in the in-utero period.

Expression of allergic diseases in very early childhood indicates that early life events play a significant role in childhood allergy development. The developmental origins of allergy hypothesis suggest events initiated in the in-utero period derived from the interaction between maternal, placental, and fetal factors may contribute to childhood allergy susceptibility. Environmental impacts on placental function and fetal programming are imperative in defining illness risk during pregnancy. Fetal programming, a process by which an injury delivered during a critical period of development, causes immediate adaptive responses with long-term consequences on an organism's structure or function. During pregnancy, the maternal immune response is skewed towards Th2-related humoral responses, hence increasing the susceptibility of childhood allergy development. Maternal atopic phenotype markedly increases the probability of her offspring developing an allergic predisposition. Combination of in utero events - which include maternal asthma or infection, and exposures to maternal allergy which changes the placental function - can alter placental cytokine expression and could predispose offspring to an allergic phenotype. All these events may affect embryology and fetal immune system development. Interestingly, the mechanism and role of the in-utero events on the developmental origins of allergy are not clearly understood; this will be addressed in this review. (199 words).

Management of evidence and conflict of interest in guidelines on early childhood allergy prevention and child nutrition: study protocol of a systematic synthesis of guidelines and explorative network analysis.

Background: With the rising prevalence of allergic diseases in children, prevention of childhood allergies becomes an important public health issue. Recently, a paradigm shift is taking place in the approach to preventing allergies, and clinical practice guidelines (CPG) and food-based dietary guidelines (FBDG) play an important role in providing practitioners with the latest evidence and reliable guidance. However, concern about the methodological quality of the development of FBDGs and CPGs, including limitations in the systematic reviews, lack of transparency and unmanaged conflicts of interest (COI), reduce the trust in these guidelines. Methods: We aim to synthesize the available guidance on early childhood allergy prevention (ECAP) through a systematic search for national and international CPGs and FBDGs concerning ECAP and child nutrition (CN) and to assess the quality of the guidelines and management of COI. Additionally, we will analyse the content and the evidence base of the recommendation statements. We aim to quantify the COI in guideline panellists and explore possible associations between COI and recommendations. Through a social network analysis, we expect to elucidate ties between panellists, researchers, institutions, industry and other sponsors. Guidelines are an important tool to inform healthcare practitioners with the newest evidence, but quality and reliability have to be high. This study will help identify potential for further improvement in the development of guidelines and the management of COI. If the social network analysis proves feasible and reveals more information on COI in comparison to disclosed COI from the previous analyses, the methodology can be developed further to identify undisclosed COIs in panelists. Ethics and dissemination: This research does not require ethical approval because no human subjects are involved. Results will be published in international peer-reviewed open access journals and via presentations at scientific conferences.

The evidence for interventions in early childhood allergy prevention - towards a living systematic review: protocol.

Background: Research in early childhood allergy prevention (ECAP) is flourishing and new intervention strategies have proven to be promising. Due to the dynamic nature of ECAP, gaps between what is known and how guidelines inform practice are likely. A living systematic review (LSR) can narrow this gap by incorporating new evidence as it becomes available. No efficacy comparisons across various ECAP interventions for similar outcomes have been carried out. Networks of randomised clinical trials can be evaluated in the context of a network meta-analysis (NMA). We aim to establish a LSR on the efficacy and safety of any intervention investigated in randomised controlled trials (RCT) to prevent the occurrence of allergic sensitisation (AS), symptoms or diagnoses of allergic diseases in infancy and early childhood (0-3 years). Methods: A baseline SR will synthesise the evidence from existing SRs of RCTs as well as RCTs not yet considered in these. After completion of the baseline SR we propose to conduct a LSR. Using this methodology, we aim to undertake constant evidence surveillance, three-monthly search updates, and review updates every three months, should new evidence emerge. Conclusions: The ECAP evidence landscape has undergone dramatic transformations and this process is likely to continue. As a response to this, a LSR offers the potential to allow more timely synthesis of new evidence as it emerges. Long gaps between updates of SRs makes it harder for guidelines and recommendations to be up to date. Users of information, such as parents, may be confused if they encounter new evidence that is not part of a trusted guideline. A LSR approach allows us to continuously search the literature and update the evidence-base of existing ECAP interventions resulting in a decreased timespan from evidence accrual to informing clinical practice.

Pre-Conception Maternal Food Intake and the Association with Childhood Allergies.

BACKGROUND: Periconceptional nutrition may have an important function in programming the immune function and allergies, however, there is a lack of studies assessing pre-conception food intake and childhood allergic disorders. The aim of the current study was to identify maternal pre-conception dietary components that may be associated with allergic disorders in children up to 3 years of age. METHODS: Pregnant women attending their first antenatal visit and who were aged >18 years were invited to participate. Pre-conception food frequency data was retrospectively collected at 18 weeks' gestation. Childhood eczema, current wheeze, and rhinitis was assessed at 36 months of age using a questionnaire and doctor diagnosis (n = 234). Linear discriminant analysis (LDA) was used to explore the combination of dietary food components that best discriminated between allergy status in children. RESULTS: Maternal pre-conception food intake such as low and high fat dairy, fresh fruit, unsaturated spreads, and take-away foods, were protective for any allergy assessed. Non-oily fish was protective for eczema and current wheeze; saturated spreads (e.g., butter) was protective for eczema, current wheeze, and rhinitis; poultry and fruit juice were adversely associated with each allergy. CONCLUSIONS: Pre-conception food intakes demonstrate inconsistent and somewhat contrary relationships to the development of child allergies. Whether and how maternal food intake impacts the underlying fetal programming and the mechanisms of childhood allergy warrants further investigation.

Epigenome-wide association study reveals methylation pathways associated with childhood allergic sensitization.

Epigenetic mechanisms integrate both genetic variability and environmental exposures. However, comprehensive epigenome-wide analysis has not been performed across major childhood allergic phenotypes. We examined the association of epigenome-wide DNA methylation in mid-childhood peripheral blood (Illumina HumanMethyl450K) with mid-childhood atopic sensitization, environmental/inhalant and food allergen sensitization in 739 children in two birth cohorts (Project Viva-Boston, and the Generation R Study-Rotterdam). We performed covariate-adjusted epigenome-wide association meta-analysis and employed pathway and regional analyses of results. Seven-hundred and five methylation sites (505 genes) were significantly cross-sectionally associated with mid-childhood atopic sensitization, 1411 (905 genes) for environmental and 45 (36 genes) for food allergen sensitization (FDR<0.05). We observed differential methylation across multiple genes for all three phenotypes, including genes implicated previously in innate immunity (DICER1), eosinophilic esophagitis and sinusitis (SIGLEC8), the atopic march (AP5B1) and asthma (EPX, IL4, IL5RA, PRG2, SIGLEC8, CLU). In addition, most of the associated methylation marks for all three phenotypes occur in putative transcription factor binding motifs. Pathway analysis identified multiple methylation sites associated with atopic sensitization and environmental allergen sensitization located in/near genes involved in asthma, mTOR signaling, and inositol phosphate metabolism. We identified multiple differentially methylated regions associated with atopic sensitization (8 regions) and environmental allergen sensitization (26 regions). A number of nominally significant methylation sites in the cord blood analysis were epigenome-wide significant in the mid-childhood analysis, and we observed significant methylation - time interactions among a subset of sites examined. Our findings provide insights into epigenetic regulatory pathways as markers of childhood allergic sensitization.