To the Editor,
‘Dietary diversity’ (DD), is defined as the number of different foods or food groups consumed over a given reference period1. A report from the European Academy of Asthma, Allergy and Immunology found that increased DD may reduce the risk for development of food and aero-allergen sensitization via its effect on the microbiome and increased intake of immune-modulatory nutrients2. The report summarized 14 papers reporting the role of DD on allergy outcomes. Only two studies reported on the association between increased DD and food allergen sensitisation3,4, one of which found a reduced risk4. One study reported an association between increased DD and decreased aero-allergen sensitization4.
The aim of this study is to assess the effect of DD in the first year of life on food and aero allergen sensitization over the first ten years of life in a population birth cohort.The Food Allergy and Intolerance Research (FAIR) birth cohort included children born on the Isle of Wight (UK) (n = 969) between 2001-2002 who were followed up prospectively3. Demographic and reported familial allergy data were collected at 12 weeks gestation using the validated ISAAC questions4 . Infant and child allergy data was collected at 3, 6, 9 months and 1, 2, 3 and 10 years.
Food introduction data were collected via a standardized questionnaire at ages 3, 6, and 9 months5. Specific information was collected regarding breastfeeding duration, introduction of infant formula feeding and age of introduction of 21 foods categorized at the same time periods7. The 21 foods were fruits (citrus fruit, non-citrus fruit, strawberries, tomato), vegetables, potato, pulses, non-wheat cereals (rice, oats), meat (chicken/turkey, lamb, beef, pork) and food allergens (cows’ milk products, egg, wheat, peanut, tree nuts, fish, soy and sesame). DD was calculated as the number of foods introduced by 3, 6, and 9 months. Cumulative DD was calculated as the number of different foods eaten by 6 months plus number of foods eaten by 9 months6,7. Portion size and frequency of intake data was not available.
Skin prick tests (SPT) were performed to milk, wheat, egg, cod, peanut and sesame at 1, 2, 3 and 10 years. A new variable was calculated for children diagnosed with any food sensitization in the first ten years of life (“over the first ten years”). The following aeroallergens were tested via SPT at the same time points: house dustmite, cat and grass. Ethical approval was obtained from the NRES South Central - Southampton B Research Ethics Committee (REF 10/H0504/11). All parents consented and children provided assent.
Data were double entered on SPSS versions 20 and 21 (SPSS Inc, Chicago, USA). Descriptive statistics with means (standard deviations) or counts (frequencies) were calculated. Univariate analysis was carried out to assess the associations between DD, food and aero allergen sensitization. Logistic regression models were fitted to describe the relationship between the binary food sensitization variables, DD and other related covariates. If independent variables (family history of allergic disease, maternal history of food sensitization and food allergy, parity, maternal smoking prior to pregnancy, breastfeeding duration, timing of introduction of solid foods, and any eczema in the first year of life) were found to be statistically significant at the p=0.05 level in the univariate analysis, the variables were entered into a multivariate model to understand the variables at each time point that are independently associated with food sensitization in the first 10 years of life. Spearman correlations were performed to examine relationships between count data. All significance tests were two sided and analyses were performed with SAS version 9.4 (SAS Institute Inc., Cary, NC, USA). We made no adjustments for multiple comparisons because the hypotheses were made a priori .
Data was available on 851 mother-infant dyads, for whom we had information on DD, food and aero allergen sensitization on at least one occasion up to 10 years of age. There were 763 (89.7%) children with data at 1 year, 658 (77.3%) at 2 years, 670 (78.7%) at 3 years and 589 (69.2%) at 10 years. Demographic, environmental and allergic characteristics are shown in Table 1.
The DD by 3, 6 and 9 months was 0 (IQR 0), 11 (IQR 9-13) and 16 (IQR 14-17). Cumulative DD at 6+9 months was 27 (IQR 24-30). Table 2 shows the univariate results for the associations between DD and food sensitization at each time point. A higher DD at 6 months decreased the odds of food sensitization at 1 year (OR 0.86, 95%CI 0.74-1.0, p=0.04), 2 years (OR 0.84, 95%CI 0.73-0.96, p=0.01) and over the first 10 years combined (OR 0.92, 95% CI 0.88-0.98, p=0.01). Likewise, a higher DD at 9 months decreased the odds of food sensitization at 2 (OR 0.81, 95%CI 0.67-0.98), p=0.03) and 3 years (OR 0.83, 95% CI 0.7-0.98, p=0.03) (Figure 1). A higher cumulative DD (6+9 months) decreased the odds of food sensitization at 1, 2 and 3 years. There was no association between DD at any age and food sensitization at 10 years.
Looking at covariates, maternal history of food sensitization, parity, maternal prenatal smoking, later introduction of solid foods and eczema in the first year of life were associated with food sensitization at one or more time periods (supplementary file 1). In the multivariate model (Table 2) a higher DD at 6 months decreased the odds of food sensitization at 1 year (OR 0.79, 95%CI 0.65-0.96, p=0.02) and 2 years (OR 0.84, 95% CI 0.73-0.96, p=0.01). A higher DD at 9 months decreased the odds of food sensitization at 2 years (OR 0.79, 95%CI 0.65-0.96, p=0.02), but not at any other age. A higher cumulative DD decreased the odds of food sensitization at 1 and 2 years. There was no association between DD at any age and aeroallergen sensitization at any age (data not shown).
Overall our data demonstrates a reduced risk of food sensitization up to 2 years of age in those consuming a higher diversity of foods in the first 6-9 months of life. On the whole, the association was maintained when relevant confounding variables were accounted for, but was not apparent at age 10 in either the univariate or multivariate analyses. This aligns to some extent with research by Roduit et al.6 and Markevyech et al.8, who used similar methods and study designs, thus adding support to the evidence base promoting dietary exposure in early life to prevent food allergy, rather than dietary avoidance.
Roduit et al.6, included participants from 5 European countries, with a similar sample size (n=856) to the FAIR cohort. They assessed intake of a smaller number of foods (between 6-15) with children followed up at 4.5 and 6 years. In addition to a reduced risk of food sensitization, they also found that increasing infant DD was protective of asthma and was positively associated with increased expression of a marker for regulatory T cells, providing a plausible mechanism. Markeyvech et al8, using data from the German LISA cohort (n=2518), reported higher infant DD was associated with decreased risk of allergic sensitization to aeroallergens up to age 15 years among children with early skin symptoms. It is not clear why in the FAIR cohort, the reduced risk of food sensitization exists until age 2, but not until age 10, as in the case of clinical food allergy9, or why we did not find an association with aeroallergen sensitization. This may be due to a more pronounced effect on the microbiome in the first 1-3 years of life than in later childhood10. Early life microbiome has particularly been associated with early life food allergen sensitization11. Differences in aeroallergen sensitization may be due to different range of allergens tested.
Strengths of this study are the prospective design, large numbers of foods considered and low attrition rate. Although we considered a range of confounding variables, there may be unknown or unmeasured factors that we have not explored. In summary, higher food diversity during the first 6-9 months of life is associated with a decreased risk of food allergic sensitization up to 2 years of age in adjusted models and up to 3 years of age in unadjusted models in our population based cohort.
Kate Maslin PhD1,2,
Kaci Pickett MSc3,
Suzanne Ngo3,4 MD,
William Anderson3,4 MD,
Taraneh Dean PhD2,5,
Carina Venter PhD2,3,4
1.School of Nursing and Midwifery, University of Plymouth, Plymouth, UK.
2.The David Hide Asthma and Allergy Centre, St. Mary’s Hospital, Isle of Wight, UK
3.University of Colorado School of Medicine, Colorado, USA
4.Allergy and Immunology Section, Children’s Hospital Colorado, Colorado, USA
5.University of Brighton, Brighton, UK
Acknowledgements: We thank all the FAIR study participants and families for their participation over the years.
Impact statement: Higher food diversity during the first 6-9 months of life is associated with a decreased risk of food allergic sensitization up to 2 years of age in adjusted models and up to 3 years of age in unadjusted models, providing further evidence that a varied infant diet should be encouraged.