S3 guideline Allergy Prevention.

BACKGROUND: The persistently high prevalence of allergic diseases in Western industrial nations and the limited possibilities of causal therapy make evidence-based recommendations for primary prevention necessary. METHODS: The recommendations of the S3 guideline Allergy Prevention, published in its last version in 2014, were revised and consulted on the basis of a current systematic literature search. The evidence search was conducted for the period 06/2013 - 11/2020 in the electronic databases Cochrane and MEDLINE, as well as in the reference lists of current reviews and through references from experts. The literature found was screened in two filtering processes, first by title and abstract, and the remaining papers were screened in the full text for relevance. The studies included after this were sorted by level of evidence, and the study quality was indicated in terms of potential bias (low/high). The revised recommendations were formally agreed and consented upon with the participation of representatives of the relevant professional societies and (self-help) organizations (nominal group process). Of 5,681 hits, 286 studies were included and assessed. RESULTS: Recommendations on maternal nutrition during pregnancy and breastfeeding as well as on infant nutrition in the first months of life again play an important role in the updated guideline: Many of the previous recommendations were confirmed by the current data. It was specified that breastfeeding should be exclusive for the first 4 - 6 months after birth, if possible, and that breastfeeding should continue with the introduction of complementary foods. A new recommendation is that supplementary feeding of cow's milk-based formula should be avoided in the first days of life if the mother wishes to breastfeed. Furthermore, it was determined that the evidence for a clear recommendation for hydrolyzed infant formula in non-breastfed infants at risk is currently no longer sufficient. It is therefore currently recommended to check whether an infant formula with proven efficacy in allergy prevention studies is available until the introduction of complementary feeding. Finally, based on the EAACI guideline, recommendations were made for the prevention of chicken egg allergy by introducing and regularly giving thoroughly heated (e.g., baked or hard-boiled) but not "raw" chicken egg (also no scrambled egg) with the complementary food. The recommendation to introduce peanut in complementary feeding was formulated cautiously for the German-speaking countries: In families who usually consume peanut, the regular administration of peanut-containing foods in age-appropriate form (e.g., peanut butter) with the complementary diet can be considered for the primary prevention of peanut allergy in infants with atopic dermatitis (AD). Before introduction, a clinically relevant peanut allergy must be ruled out, especially in infants with moderate to severe AD. There is still insufficient evidence for an allergy-preventive efficacy of prebiotics or probiotics, vitamin D, or other vitamins in the form of supplements so that recommendations against their supplementation were adopted for the first time in the current guideline. Biodiversity plays an important role in the development of immunological tolerance to environmental and food allergens: there is clear evidence that growing up on a farm is associated with a lower risk of developing asthma and allergic diseases. This is associated with early non-specific immune stimulation due to, among other things, the greater microbial biodiversity of house dust in this habitat. This aspect is also reflected in the recommendations on animal husbandry, on which a differentiated statement was made: In families without a recognizable increased allergy risk, pet keeping with cats or dogs should not generally be restricted. Families with an increased allergy risk or with children with already existing AD should not acquire a new cat - in contrast, however, dog ownership should not be discouraged. Interventions to reduce exposure to dust mite allergens in the home, such as the use of mite allergen-proof mattress covers ("encasings"), should be restricted to patients with already proven specific sensitization against house dust mite allergen. Children born by caesarean section have a slightly increased risk of asthma - this should be taken into account when advising on mode of delivery outside of emergency situations. Recent work also supports the recommendations on air pollutants: Active and passive exposure to tobacco smoke increase the risk of allergies, especially asthma, and should therefore be avoided. Exposure to nitrogen oxides, ozone, and small particles (PM 2.5) is associated with an increased risk, especially for asthma. Therefore, exposure to emissions of nitrogen oxides, ozone, and small particles (PM 2.5) should be kept low. The authors of this guideline are unanimously in favor of enacting appropriate regulations to minimize these air pollutants. There is no evidence that vaccinations increase the risk of allergies, but conversely there is evidence that vaccinations can reduce the risk of allergies. All children, including children at risk, should be vaccinated according to the current recommendations of the national public health institutes, also for reasons of allergy prevention. CONCLUSION: The consensus of recommendations in this guideline is based on an extensive evidence base. The update of the guideline enables evidence-based and up-to-date recommendations for the prevention of allergic diseases including asthma and atopic dermatitis.

Dietary Macronutrient Composition in Relation to Circulating HDL and Non-HDL Cholesterol: A Federated Individual-Level Analysis of Cross-Sectional Data from Adolescents and Adults in 8 European Studies.

BACKGROUND: Associations between increased dietary fat and decreased carbohydrate intake with circulating HDL and non-HDL cholesterol have not been conclusively determined. OBJECTIVE: We assessed these relations in 8 European observational human studies participating in the European Nutritional Phenotype Assessment and Data Sharing Initiative (ENPADASI) using harmonized data. METHODS: Dietary macronutrient intake was recorded using study-specific dietary assessment tools. Main outcome measures were lipoprotein cholesterol concentrations: HDL cholesterol (mg/dL) and non-HDL cholesterol (mg/dL). A cross-sectional analysis on 5919 participants (54% female) aged 13-80 y was undertaken using the statistical platform DataSHIELD that allows remote/federated nondisclosive analysis of individual-level data. Generalized linear models (GLM) were fitted to assess associations between replacing 5% of energy from carbohydrates with equivalent energy from total fats, SFAs, MUFAs, or PUFAs with circulating HDL cholesterol and non-HDL cholesterol. GLM were adjusted for study source, age, sex, smoking status, alcohol intake and BMI. RESULTS: The replacement of 5% of energy from carbohydrates with total fats or MUFAs was statistically significantly associated with 0.67 mg/dL (95% CI: 0.40, 0.94) or 0.99 mg/dL (95% CI: 0.37, 1.60) higher HDL cholesterol, respectively, but not with non-HDL cholesterol concentrations. The replacement of 5% of energy from carbohydrates with SFAs or PUFAs was not associated with HDL cholesterol, but SFAs were statistically significantly associated with 1.94 mg/dL (95% CI: 0.08, 3.79) higher non-HDL cholesterol, and PUFAs with -3.91 mg/dL (95% CI: -6.98, -0.84) lower non-HDL cholesterol concentrations. A statistically significant interaction by sex for the association of replacing carbohydrates with MUFAs and non-HDL cholesterol was observed, showing a statistically significant inverse association in males and no statistically significant association in females. We observed no statistically significant interaction by age. CONCLUSIONS: The replacement of dietary carbohydrates with fats had favorable effects on lipoprotein cholesterol concentrations in European adolescents and adults when fats were consumed as MUFAs or PUFAs but not as SFAs.

Growth rate of coeliac children is compromised before the onset of the disease.

INTRODUCTION: Growth impairment has often been described in children who develop coeliac disease (CD). Based on data from the multicentre, longitudinal PreventCD study, we analysed the growth patterns of infants at genetic risk of CD, comparing those who developed CD by 6 years of age (CD 'cases', 113 infants) versus those who did not develop CD by 6 years (no CD 'controls', 831 infants). METHODS: Weight and length/height were measured using a longitudinal protocol. Raw measurements were standardised, computing z-scores for length/height and weight; a linear mixed model was fitted to the data in order to compare the rate of growth in the two cohorts. RESULTS: Neither cases nor controls had significant growth failure. However, when the mean z-scores for weight and height were analysed, there was a difference between the two groups starting at fourth month of life. When the growth pattern in the first year was analysed longitudinally using mixed models, it emerged that children who develop CD had a significantly lower growth rate in weight z-score (-0.028/month; 95% CI -0.038 to -0.017; p<0.001) and in length/height z-score (-0.018/month; 95% CI -0.031 to -0.005; p=0.008) than those who do not develop CD. When the whole follow-up period was analysed (0-6 years), differences between groups in both weight and length/height z-scores were confirmed. CONCLUSION: The growth of children at risk of CD rarely fell below 'clinical standards'. However, growth rate was significantly lower in cases than in controls. Our data suggest that peculiar pathways of growth are present in children who develop CD, long before any clinical or serological signs of the disease appear.

Impact on parents of HLA-DQ2/DQ8 genotyping in healthy children from coeliac families.

Due to the association of coeliac disease and HLA-specificities DQ2 and DQ8, HLA-typing can be used for risk determination of the disease. This study was designed to evaluate the knowledge of parents from coeliac families regarding HLA-typing and the impact of HLA-typing on the perception of the health of their children. A structured questionnaire was sent to the Dutch, Spanish and German parents participating with their child in the European PreventCD study on disease prevention in high-risk families, addressing parents' understanding of and attitude towards HLA-typing, distress related to HLA-typing and perceived health and health-related quality of life of their children. Sixty-eight percent of parents of 515 children returned the questionnaires, with 85% of children being DQ2/DQ8 positive. The majority of all parents answered the questions on knowledge correctly. Forty-eight percent of parents of DQ2/DQ8-negative children thought their child could develop coeliac disease. More distress was reported by parents of DQ2/DQ8-positive children (P<0.001). All parents showed few regrets and would repeat HLA-typing in future children. Perceived health and health-related quality of life were similar. In conclusion, we can say that misinterpretation of DQ2/DQ8-negative results by parents is frequent. DQ2/DQ8-positive results do not affect perceived health and health-related quality of life of children but may cause temporary negative feelings among parents. Parents of coeliac families seem to support HLA-typing.

Respiratory diseases are associated with molar-incisor hypomineralizations.

The objective of our study was to evaluate the association of molar-incisor hypomineralizations (MIHs) with prospectively collected potential causative factors from the first 4 years of life, e.g. respiratory diseases, breastfeeding, maternal smoking and parental education. A total of 692 children (10 years old) from the GINI birth cohort study participated. The dental examination included the registration of enamel hypomineralizations (EHs) according to the EAPD criteria. Children with EH were sub-categorized into those with at least one EH (MIH/1), those with a minimum of one EH on at least one first permanent molar (MIH/2) and those with EH on at least one first permanent molar and a permanent incisor (MIH/3). All relationships between causative factors and caries or MIH were evaluated using simple and multiple logistic regression analyses. EHs were observed in 37.9% (MIH/1), 14.7% (MIH/2) and 9.2% (MIH/3) of all subjects. After adjustment for confounding factors, 10-year-old children with at least one episode of respiratory disease had a significantly higher risk (2.48 times, adjusted OR) for the development of MIH/3. In case of breastfeeding, a non-significant association was observed. None of the tested factors was associated with either MIH/1 or MIH/2. Early respiratory diseases seem to be directly or indirectly related to MIH/3 only. The role of (systemic) medications used for treatment of these diseases needs to be investigated in future studies.

Proportion and extent of manifestation of molar-incisor-hypomineralizations according to different phenotypes.

OBJECTIVE: This epidemiological study aimed to assess the proportion and extent of manifestation of enamel hypomineralization, including molar-incisor-hypomineralization (MIH), in the permanent and primary dentition. METHODS: A total of 693 children enrolled in an ongoing birth cohort study (GINIplus-10) were examined at their 10-year follow-up. Enamel hypomineralization was scored in the primary and permanent dentition on a tooth- and surface-related level based on the criteria of the European Academy of Paediatric Dentistry (EAPD). Children were grouped according to their distribution pattern of enamel hypomineralization: children with a minimum of one hypomineralized tooth in the primary dentition (ht ≥ 1) and permanent dentition (HT ≥ 1); with a minimum of one hypomineralization on at least one first permanent molar (MIH); and with hypomineralization on at least one first permanent molar and permanent incisor (M + IH). For each group, the mean values of hypomineralized primary teeth (ht), permanent teeth (HT), and permanent surfaces (HS) were calculated. RESULTS: The proportion of affected children was 36.5 percent (HT ≥ 1), 14.7 percent (MIH), and 9.4 percent (M + IH); 6.9 percent of the subjects had a minimum of one affected primary tooth (ht ≥ 1). The mean number of hypomineralized permanent teeth and surfaces were 2.3HT/2.9HS (HT ≥ 1), 3.4HT/4.8HS (MIH), and 4.2HT/5.9HS (M + IH). The mean number of hypomineralized primary teeth amounted to 0.1ht in the entire study population. CONCLUSIONS: Enamel hypomineralization can be detected frequently in this study sample. Children with M + IH showed the highest number of affected teeth and surfaces followed by those with MIH.