Carina Venter

The Milk Allergy in Primary (MAP) Care guideline was first published in 2013 in this journal. MAP aimed to provide simple and accessible algorithms for UK clinicians in primary care, detailing all the steps between initial presentation, through diagnosis, management and tolerance development. Despite its UK focus, it soon became clear that MAP was being accessed internationally and thus an updated International Milk Allergy in Primary Care (iMAP) guideline was published in 2017. Both guidelines used existing international consensus guidelines to develop accessible algorithms accompanied by patient information leaflets. In 2018, the guidelines were criticised for 3 distinct reasons: promoting the overdiagnosis of cow’s milk allergy (CMA), negatively impacting breastfeeding and the possibility of industry influence on the guidelines. The authors address these criticisms using available evidence and, in the context of this and in consultation with patient groups, members of the General Practice Infant Feeding Network and other infant feeding healthcare leads, have collaboratively produced updated algorithms and an information leaflet to support breastfeeding. We believe iMAP is now closer to its original aim of facilitating early and accurate diagnosis of CMA, whilst minimising, as far as possible, any concerns around overdiagnosis or a risk to breastfeeding rates. We continue to welcome open and constructive engagement about how best to achieve these aims to provide evidence-based, practical guidelines for the primary care practitioner.

Evidence suggests that prenatal exposure to n-3 long-chain polyunsaturated fatty acids (LCPUFA) reduces the incidence of allergic disease in children. LCPUFAs are produced from dietary precursors catalyzed by desaturases and elongases encoded by the FADS1/2 and ELOVL5 genes. DNA methylation regulates gene activity and fatty acid supplementation could alter DNA methylation (DNA-M) at these genes. We investigated whether DNA-M and expression of the FADS1/2 and ELOVL5 genes were associated with allergy in children and gestational fish intake. We studied 170 participants from the Isle of Wight 3rd Generation Cohort, UK. Phenotype data and exposure was assessed by questionnaires. Genome-wide DNA-M in cord blood samples was quantified using the Illumina Infinium HumanMethylation450 and EPIC Beadchips. Five SNPs (single-nucleotide polymorphisms) in the FADS gene cluster and one SNP in ELOVL5 were genotyped in offspring. FADS gene expression in offspring cord blood was determined. Gestational fish intake was significantly associated with increased methylation of cg12517394 (P = 0.049), which positively correlated with FADS1 mRNA levels (P = 0.021). ELOVL5 rs2397142 was significantly associated with eczema (P = 0.011) and methylation at cg11748354 and cg24524396 (P < 0.001 and P = 0.036, respectively). Gestational fish intake was strongly associated with elevated DNA-M at cg11748354 and cg24524396 (P = 0.029 and P = 0.002, respectively) and reduced ELOVL5 mRNA expression (P = 0.028). The association between induced FADS1/2 and ELOVL5 DNA-M and reduced gene expression due to gestational fish intake provide a mechanistic explanation of the previously observed association between maternal LCPUFA intake and allergy development in early childhood.

As the prevalence of allergic disease dramatically rises worldwide, prevention strategies are increasingly being considered. Given the potential modulatory effect of nutritional factors on disease, altering maternal diet during pregnancy and/or lactation has been considered in preventing allergic disease in offspring. Although there are a number of observational studies that have examined possible associations between maternal diet and allergic outcomes in offspring, interventional trials are limited. Furthermore, there is a paucity of studies that have prospectively studied maternal dietary intake as well as measuring maternal and infant biologic samples (blood, urine, breast milk) and their relation to allergic outcomes in infants. There is also a particular need to define terminology such as ‘fruit and vegetables intake’, ‘healthy diet’, and ‘diet diversity’ in order to make studies comparable. In this review, we discuss current evidence of maternal dietary factors during pregnancy and/or lactation that may play a role in the offspring developing allergic disease, including factors such as overall dietary intake patterns, specific whole food consumption (fish, fruit and vegetables, and common allergic foods), and individual immunomodulatory nutrient intakes. Additionally, we discuss the limitations of previous studies and propose improvements to study design for future investigation.

The timing of introduction of solid food on the subsequent development of food allergy is under debate and the role of concurrent breastfeeding is unclear. The aim of the present study was to investigate the role of solid food introduction whilst concurrently breastfeeding on food allergy outcome, with a specific focus on cows’ milk allergy. Prospectively collected infant feeding data from a birth cohort were analysed. Participants with histories suggestive of food allergy underwent diagnostic food challenges. Children with food allergy were matched to control participants for age and sex. Mann–Whitney U tests, χ², Fisher exact tests and logistic regression calculations were undertaken. A total of thirty-nine food-allergic children and seventy-eight matched controls were identified, including twenty-two cows’ milk-allergic children and forty-four matched controls. The control group introduced solid food earlier than the food-allergic group (P < 0·05). There was no effect of concurrent breastfeeding alongside cows’ milk introduction or other food allergens on the development of food allergy. Due to small numbers, it was not possible to explore differences for food allergy phenotype. We have therefore found no evidence that introducing solids, or food allergens, whilst breastfeeding has an allergy-preventative effect; however, the results should be interpreted with caution due to sample size. Recommendations regarding infant feeding and food allergy should be carefully considered. Although breastfeeding should be promoted for many health reasons, larger studies looking at the introduction of food allergens on the development of food allergy are needed to make a final conclusion.

Background: The aim of this study was to explore the natural history of peanut allergy in childhood in two birth cohorts from the same geographical region in the South of England.Methods: The FAIR birth cohort was established on the Isle of Wight (UK) between 2001 and 2002 (n = 969). Children were followed up prospectively, skin prick tested (SPT) to peanut allergens at 1, 2, 3 and 10 years and food challenges performed. The Isle of Wight (IOW) birth cohort was established in 1989 (n = 1456). SPTs were performed at 1, 2, 4 and 10 years. Peanut allergy was based on positive SPT and a good clinical history.Results: In the FAIR cohort, the prevalence of sensitization to peanut was 0.4%, 2.0%, 2.0% and 2.4% at 1, 2, 3 and 10 years, respectively. At 10 years of age, 12 of 828 (1.5%) children were diagnosed with peanut allergy. One child (8%) outgrew her peanut allergy between 3 and 10 years and two children (15%) presented with new onset peanut allergy. Over the first 10 years of life, 13 of 934 (1.4%) children were diagnosed with peanut allergy. In the IOW cohort, 6 of 1034 (0.58%) were diagnosed with peanut allergy at 10 years. We found no significant differences between the FAIR and the IOW birth cohort for any of the time points studied.Conclusion: Peanut allergy appears to be stable over the first 10 years of life in our cohorts. There was no significant difference in peanut sensitization or clinical peanut allergy between 1989 and 2001.

Patients often report adverse reactions to wheat. Interpretation of sensitization to wheat pollen and flour with/without sensitization to grass pollen is a clinical problem. We set out to determine the prevalence of wheat allergy in a birth cohort (10/11 year olds) and investigate the usefulness of performing skin prick tests (SPT), specific IgE tests and component resolved diagnostics to wheat pollen and flour. The Food Allergy and Intolerance Research (FAIR) birth cohort included babies born on the Isle of Wight (UK) between September 2001–August 2002 (n = 969). Children were followed up at 1, 2, 3 and 10/11 years. 588 children had SPTs to wheat pollen and grass during the 10 year follow-up. 294 children underwent further SPT to wheat flour and 246 had specific IgE testing to wheat and grass. Eight children underwent oral food challenges (OFC). We diagnosed 0.48 % (4/827; 95 % CI 0–1 %) children with wheat allergy based on OFC. 16.3 % (96/588) were sensitized to grass pollen, 13.4 % (79/588) to wheat pollen; 78 % (75/96) sensitized to both. Only one child was sensitized to wheat flour and wheat pollen, but not grass pollen. For specific IgE, 15.0 % (37/246) and 36.2 % (89/246) were sensitized to wheat and grass pollen, with 40.5 % (36/89) sensitized to both. Of the 37 children sensitized to wheat, 3 (8.1 %) were sensitized to omega 5 gliadin, 1 (2.7 %) to wheat lipid transfer protein and 1 to wheat gliadin. Clinicians should be aware of the high level of cross-sensitization when performing tests to wheat and grass pollen i.e. sensitisation to wheat specific IgE and wheat pollen SPT should be assessed in the presence of grass pollen SPT and/or specific IgE.

Infants with suspected cows’ milk allergy are required to follow a strict milk exclusion diet which may lead to nutritional deficiencies, especially if not supervised by a healthcare professional. The aim of this study was to assess the nutritional adequacy of a cows’ milk exclusion diet in a group of UK infants over a period of 6 months. Participants in this study are a subgroup of the Prevalence of Infant Food Allergy study, a prospective food allergy birth cohort study from the South of England. Each infant consuming a milk free diet, following advice from a specialist allergy dietitian, was matched to two control infants who were consuming an unrestricted diet, forming a nested matched case–control study. Detailed food diaries completed prospectively for 1 week per month over a 5 month period, were coded and analysed according to a standard protocol. The diets of 39 infants (13 milk-free and 26 controls) were assessed. Mean age at diet commencement was 14 weeks. Two of the eleven infants started on an extensively hydrolysed formula did not tolerate it and required an amino acid formula for symptom resolution. All infants had mean intakes in excess of the estimated average requirement for energy and the recommended nutrient intake (RNI) for protein, calcium, iron, selenium, zinc, vitamins A, C and E. Vitamin D intake was in excess of the RNI at all time-points, except at 44 weeks of age. Across the study period, selenium intake was higher for infants consuming a milk free diet whilst vitamin C intake was higher for infants consuming an unrestricted diet. Differences were found between the two groups for protein, calcium, iron and vitamin E intakes at differing time points. This study demonstrated that although infants consuming a milk-free diet have a nutritional intake that is significantly different to matched controls who are eating an unrestricted diet, this difference is not constant and it is not seen for all nutrients. Further research in infants without dietetic input is needed to explore the nutritional implications of unsupervised cows’ milk exclusion diets.

Background: Prevalence, incidence and natural history of food hypersensitivity (FHS) and its trends in an unselected cohort of older children are unclear.Methods: A birth cohort born on the Isle of Wight (UK) between 2001 and 2002 was followed up prospectively. Children were clinically examined and skin prick tested at set times and invited for food challenges when indicated. At 10 years of age, children were also invited for a blood test.Results: A total of 969 children were recruited at 12 weeks of pregnancy, and 92.9%, 88.5%, 91.6% and 85.3% were assessed at 1, 2, 3 and 10 years. Prevalence of sensitization to any allergen over 10 years was 186 of 969 (19.2%; 95% CI: 16.84–21.8) and 108 of 969 (11.2%; 95% CI: 9.31–13.29) children were sensitized to at least one predefined food allergen. Excluding wheat (due to cross‐reactivity with pollen), 40 of 969 (4.1%; 95% CI: 3.19–5.32) children were sensitized to a predefined food allergen. Using food challenges and/or a good clinical history, the cumulative incidence of food hypersensitivity (FHS) in the first decade of life was 64 of 947 (6.8%, 95% CI: 5.2–8.4), while the prevalence of FHS at 10 years was 30 of 827 (3.6%, 95% CI: 2.54–5.15). The vast majority, 25 of 827 (3.0%, 95% CI: 1.8–4.2), suffered from IgE‐mediated food allergy, while 5 of 827 (0.6%, 95% CI: 0.07–1.3) had non‐IgE‐mediated food allergy/food intolerance.Conclusions: By the age of 10 years, 6.8% of children suffered from FHS based on food challenges and a good clinical history. There was a large discrepancy between reported and diagnosed FHS.