Desensitisation to cow’s milk, following partially or extensively hydrolysed formulae feeding regimens, in infants with allergy to cow’s milk: the DREAM RCT Synopsis (The DREAM study)
Bibliographic record
Abstract
Background Immunoglobulin E-mediated (immediate) cow’s milk allergy is one of the most frequent food allergies in infants, with a significant adverse impact on quality of life. There is no satisfactory treatment for cow’s milk allergy, and guidelines recommend milk avoidance, feeding with ‘hypoallergenic’ formulas (extensively hydrolysed formulas), emergency management of accidental reactions and waiting for the allergy to resolve spontaneously. Currently, the only potentially curative regimen is oral immunotherapy, that is, exposing patients to increasing doses of cow’s milk using a strictly controlled dose schedule. However, milk immunotherapy is not used in clinical practice due to risk of reactions. DREAM’s intention was to explore whether oral immunotherapy with a partially hydrolysed cow’s milk formula would be able to provide a safe and effective means of oral immunotherapy for milk-allergic infants. Limitations The trial was affected by a serious breach that led most of the participants to receive partially hydrolysed formula, even if randomised to extensively hydrolysed formula. It also ended prematurely due to unsatisfactory recruitment, and the main outcomes were not reached. Methods DREAM was a two-arm, parallel-group, double-blind randomised controlled trial. Eligible patients were infants aged 6–12 months with convincing medical history of immunoglobulin E-mediated allergy to cow’s milk formula. Inclusion criteria included a titre of cow’s milk-specific immunoglobulin E equal or higher to 2 kU/l, or wheal equal or over 5 mm to skin prick test to milk. Additionally, for the infants to be randomised, they needed to have a positive result to an open oral challenge either to partially hydrolysed formula or to milk. Participants were randomised to extensively hydrolysed formula or partially hydrolysed formula with a 1 : 1 ratio. Following randomisation, participants commenced free-feeding with the blinded product (or strict dose-based oral immunotherapy if they were not tolerant of the blinded product). The main outcome was the result of a double-blind, placebo-controlled food challenge to cow’s milk at the end of 1 year of free-feeding (or of dose-based immunotherapy) to establish if infants had become tolerant. As the trial was discontinued early on account of poor recruitment, no infant progressed to the double-blind, placebo-controlled food challenge. Results Out of 16 randomised participants who underwent an initial partially hydrolysed formula challenge, only 1 (6.25%) reacted to it (95% confidence interval 00.0 to 19.6). Hence, 93.75% of the allergic infants randomised in the trial tolerated partially hydrolysed formula. All fifteen infants that were found to be partially hydrolysed formula-tolerant also received partially hydrolysed formula free-feeding at home, on account of the serious breach. As per the trial’s criteria, these infants (and all randomised participants) were shown to be allergic to cow’s milk via either a positive open challenge to it (for the 15 partially hydrolysed formula-tolerant infants) or a positive open challenge to partially hydrolysed formula (for the single partially hydrolysed formula-reactive infant). Conclusions Partially hydrolysed formula was tolerated by the majority of well-characterised and confirmed cow’s milk-allergic infants in the DREAM trial. Future work Our findings demonstrate that partially hydrolysed formula holds promise as a potential oral immunotherapy medium in free-feeding oral immunotherapy regimens in future research. Further trials designed on the premise of partially hydrolysed formula oral immunotherapy are needed. Funding This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation programme as award number 17/60/44.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.004 | 0.006 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.005 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".