Enquiring About Tolerance (EAT) study: Feasibility of an early allergenic food introduction regimen

Abstract

Background: The influence of early exposure to allergenic foods on the subsequent development of food allergy remains uncertain.

Objective: We sought to determine the feasibility of the early introduction of multiple allergenic foods to exclusively breast-fed infants from 3 months of age and the effect on breastfeeding performance.

Methods: We performed a randomized controlled trial. The early introduction group (EIG) continued breastfeeding with sequential introduction of 6 allergenic foods: cow's milk, peanut, hard-boiled hen's egg, sesame, whitefish (cod), and wheat; the standard introduction group followed the UK infant feeding recommendations of exclusive breastfeeding for around 6 months with no introduction of allergenic foods before 6 months of age.

Results: One thousand three hundred three infants were enrolled. By 5 months of age, the median frequency of consumption of all 6 foods was 2 to 3 times per week for every food in the EIG and no consumption for every food in the standard introduction group (P < .001 for every comparison). By 6 months of age, nonintroduction of the allergenic foods in the EIG was less than 5% for each of the 6 foods. Achievement of the stringent per-protocol consumption target for the EIG proved more difficult (42% of evaluable EIG participants). Breastfeeding rates in both groups significantly exceeded UK government data for equivalent mothers (P < .001 at 6 and at 9 months of age).

Conclusion: Early introduction, before 6 months of age, of at least some amount of multiple allergenic foods appears achievable and did not affect breastfeeding. This has important implications for the evaluation of food allergy prevention strategies.

Keywords: Food allergy; allergens; breastfeeding; diet; infancy.

Fig E1

EAT study food frequency questionnaire.

Fig E2

EIG compliance status and early introduction of allergenic foods. The mean dose of allergenic protein consumed each week from enrollment to 12 months of age for each allergenic food is presented for the EIG group. The EIG group is divided into those who were overall compliant (34%; blue line), those who were overall noncompliant (47%; red line), and those in whom compliance was nonevaluable (19%; green line). The nonevaluable EIG participants are shown to have consumption rates similar to those of the noncompliant EIG participants.

Fig E3

Influence of the number of foods consumed and the quantity and frequency of consumption on compliance in the compliance-evaluable EIG participants.

Fig E4

Example of an EIG allergenic food introduction regimen.

Fig 1

EAT study recruitment. *Direct mailing of families with infants aged 5 to 11 weeks in England and Wales. †Exclusively breastfed at enrollment, 37 or more weeks' gestation, singleton birth, no parental report of major health concerns, not taking part in other research, willing to attend 3 study visits over a 3-year period, willing to be randomized to either study group, and not planning to move from the UK for the study's duration. ‡Reasons included concerns about participation requirements on reading of the full patient information sheet, wanting to have more flexibility with early feeding, concerns about traveling to London, child's father not happy with participation, unable to reach enrollment visit without introducing formula and/or solid food, and too many other commitments. §Eight infants randomized to each group were found to have significant health issues either on blood testing or the clinical examination at the enrollment visit rendering them ineligible for enrollment: conditions included severe vitamin D deficiency, severe iron deficiency, severe failure to thrive, familial hypercholesterolemia, congenital stridor, epidermolysis bullosa, and cartilage hair hypoplasia syndrome.

Fig 2

EAT study overview.

Fig 3

Breastfeeding in the EAT cohort. ✘, IFS2010 data. All comparisons between EIG or SIG and IFS2010 data at varying ages were statistically significant (P < .001). Data are available for exclusive breastfeeding (SIG, 633 [97.2%]; EIG, 622 [95.4%]) and any breastfeeding (SIG, 620 [95.2%]; EIG, 583 [89.4%]).

Fig 4

Consumption of allergenic foods by the EIG in the 4 weeks before their 4-, 5-, and 6-month birthdays. Data were available for 4 (581 [89.1%]), 5 (548 [84.0%]), and 6 (537 [82.4%]) months.

Fig 5

Differences in frequency of allergenic food consumption in the SIG and EIG by 4, 5, and 6 months of age. Data were available for 4 (SIG, 621 [95.4%]; EIG, 588 [90.2%]), 5 (SIG, 612 [94.0%]; EIG, 550 [84.4%]), and 6 (SIG, 605 [92.9%]; EIG, 542 [83.1%]) months. Black bar, Median; box upper hinge, 75th percentile; box lower hinge, 25th percentile; upper whisker, upper quartile + 1.5 * interquartile range; lower whisker, lower quartile − 1.5 * interquartile range. P < .0005, SIG versus EIG for every individual food at every time point.