A total of 1258 women were enrolled in the WHEALS study. Based on maternal report, 44.9% of infants had a parental history of asthma or allergy. Infants with missing information for IgE were excluded (). More participants with a history of asthma or allergy completed the 2 year visit compared to those without a history (59% vs. 52%), p=0.032 (data not shown). A total of 800 participants had completed a clinic visit at infant age 2–3 years, of which 594 (74.2%) had data for this analysis (See and Tables E1 and E2
in the online supplement). We compared maternal characteristics for women included in our analysis to that of women excluded (). No significant differences in outcomes were observed, although there were slightly more African-American/Black participants included in the analysis sample (p=0.091). Mean age for mothers in the analysis sample was 29.7 years (±5.2 years) and 60.6% were African-American/Black. is a comparison of maternal characteristics by infant age at introduction of complementary food. A higher percentage of mothers introducing complementary food at < 4 months also breastfed for less than 6 months (includes exclusive and supplemented breastfeeding), when compared to mothers who delayed introduction of complementary foods, (p<0.001).
Figure 1 Flowchart showing available data for children enrolled in the WHEALS birth cohort study and included in the analysis of the introduction of complementary food before the infant is 4 months of age and sensitization to egg, milk, or peanut by age 2–3 (more ...)
Comparison of selected maternal and infant characteristics for the WHEALS birth cohort study, by whether or not included in the analysis of age at introduction of complementary food and food sensitization
Comparison of maternal characteristics by infant age at the introduction of complementary food for members of the WHEALS birth cohort study
Prevalence of sensitization by food allergen is shown in . Overall, 40.4% of infants were sensitized (IgE≥0.35 IU/ml) to egg, milk or peanut. A higher percentage of African-American/Black infants were sensitized to these food allergens compared to Non-African-American infants, (44.1% vs. 34.7%, p=0.024). The p values for comparisons of sensitization by race for egg, milk, and peanut IgE were 0.047, 0.046, and 0.009, respectively.
Proportion of children enrolled in the WHEALS birth cohort study with serum IgE ≥ 0.35 IU/ml to egg, milk, or peanut at age 2 to 3 years.
shows the results of bivariate analysis for the association of early introduction of complementary foods to IgE sensitization for each food allergen. Overall, early complementary food was not significantly related to food sensitization. The OR for early complementary food and peanut sensitization was less than 1.0, suggesting a protective relationship (). When stratified by race, results were very similar. ORs for early complementary food and sensitization to egg or milk ranged from 0.9–1.1 (Data not shown). Early feeding trended toward an inverse association with peanut sensitization for both race groups with ORs for complementary food < 4 months and peanut IgE≥0.35 = 0.6 (0.3–1.3), p=0.166 and 0.6 (0.2–1.8), p=0.324 for African-American/Black and Non-African-American/Black, respectively (Data not shown).
Introduction of any complementary foods at < 4 months of age and IgE > 0.35 IU/ml to egg, milk or peanut by age 2–3 years among children in the WHEALS birth cohort study
shows the association between early complementary food and food sensitization, stratified by parental history of asthma or allergy, physician diagnosis of eczema by age 1 year, and food avoidance by age 1 year. The reason for the latter being that parents may have changed behavior early in infancy if symptoms were observed. Among infants with a parental history, the OR for early feeding and peanut IgE ≥ 0.35 IU/ml = 0.3 (0.1–0.8), p=0.017. Among infants with AD, none of the 7 infants fed complementary foods < 4 months had peanut IgE≥ 0.35 IU/ml, while 6 of 13 infants (53.9%) not exposed to complementary foods before 4 months had elevated IgE to peanut (p=0.051). Similarly, an inverse association was observed for infants with no report of food avoidance at 1 year, OR=0.4 (0.2–0.9), p=0.024.
Association between complementary food introduced < 4 months and IgE ≥0.35 IU/ml to egg, milk, and peanut, by factors potentially related to food avoidance before infant age 1 year among children in the WHEALS birth cohort study
We also examined the association of parental history, food avoidance by age 1 year, and AD by infant age 1 year to sensitization (Data not shown). A positive parental history was significantly related to egg sensitization, OR=1.5 (1.0, 2.3), p=0.033. Food avoidance by age 1 year was significantly related to egg sensitization, OR=3.5 (2.0–5.9), p<0.001 and to peanut sensitization, OR=4.3 (2.3–8.0), p<0.001. The relationship between atopic dermatitis by age 1 year and egg sensitization was marginally significant, OR=2.3 (0.96–5.5), p=0.055, and was significantly related to peanut sensitization, OR=3.5 (1.3–9.5), p=0.020 (Data not shown).
We felt the bivariate analyses above provided sufficient evidence that food avoidance and AD represent potential allergic manifestations along the causal pathway of food sensitization and therefore should not be included in multivariable models for which sensitization would be the dependent variable. Also based on these analyses, we analyzed egg and milk separately from peanut, using sensitization to egg or milk as the dependent variable in one logistic regression model. The p value corresponding to a test for an interaction between parental history and early feeding for egg/milk sensitization was 0.113, and was 0.146 for an interaction between parental history and early feeding for peanut sensitization.
Logistic regression models were stratified by parental report of a history of asthma or allergy. Among infants with a parental history, early introduction of complementary food was inversely related to IgE ≥ 0.35 IU/ml in both models (). This relationship was statistically significant for peanut, aOR=0.2 (0.1–0.7), p=0.007. Among infants with no parental history of asthma or allergy, early feeding was not associated with sensitization to egg/milk or peanut (). Point estimates from were similar when models were re-run using a more stringent cutoff for food allergen specific IgE (0.70 IU/ml instead of 0.35 IU/ml). Doubling the criteria for sensitization caused the relationship with early complementary food to become significant for egg, aOR=0.5 (0.3–0.9), p=0.022. Models using IgE ≥ 0.10 IU/ as the outcome resulted in an aOR=0.8 for egg/milk, but peanut remained significant at this level, aOR= 0.4 (0.2–0.9), p=0.031.
Results of logistic regression for the association of complementary foods introduced < 4 months and sensitization to milk. egg, or peanut, by parental history of asthma or allergy1 among children in the WHEALS birth cohort study
In other analyses, 2×2 tables examining the prevalence of food sensitization among children with reported early exposure to that particular food follow a pattern similar to that of the logistic regression (See Table E3
in the online supplement). ORs for exposure to egg and milk prior to 4 months of age and sensitization to egg and milk were 0.6 and 1.0 respectively; p values > 0.05. For infants exposed to peanut before 4 months of age, 0/2 (0%) with early exposure were sensitized to peanut, while 57/474 (12%) without this early exposure were sensitized to peanut. Cell sizes were too small to examine these associations by parental history of asthma or allergy. Previous studies have shown a relationship between food sensitization and atopic manifestations such as AD and wheeze.3
In our study sample, we also found that food sensitization was significantly related to AD by age 2 years for milk (p=0.015), egg (p<0.001), and peanut (p<0.001). Early complementary food, however, was not related to AD by age 2 years (OR=1.1, p=0.758). The OR for early feeding and wheeze by age 2 years suggested a reduced risk, but was not statistically significant (OR=0.6, p= 0.136).