Evidence map›Paper›PMID 41311241›Full record

ReviewClinical and translational allergy2025

Milk Ladder Efficacy and Safety in IgE-Mediated Cow's Milk Allergy: A Systematic Review and Meta-Analysis of Controlled Studies.

Barbara Cuomo, Maria Carmen Verga, Enza D'Auria, Michele Miraglia Del Giudice, Caterina Anania, Fabio Decimo, Giuliana Giannì, Giovanni Cosimo Indirli, Enrica Manca, Filippo Mondì and 4 more

Abstract readReview
In one paragraph

Review in Clinical and translational allergy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Barbara CuomoCentral Operative Unit of Pediatrics and Allergy Center for Children and Adults, "Saint Rose" Hospital, Viterbo, Italy.ORCID https://orcid.org/0000-0002-8405-780X
Maria Carmen VergaLocal Health Unit Salerno, Salerno, Italy.
Enza D'AuriaAllergy Unit, Department of Pediatrics, Buzzi Children's Hospital, Milan, Italy.ORCID https://orcid.org/0000-0003-2750-5810
Michele Miraglia Del GiudiceDepartment of Woman, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy.ORCID https://orcid.org/0000-0002-8369-5957
Caterina AnaniaDepartment of Maternal Infantile and Urological Science, Sapienza University of Rome, Roma, Italy.ORCID https://orcid.org/0000-0002-9607-8632
Fabio DecimoDepartment of Woman, Child and General and Specialized Surgery, University of Campania "L. Vanvitelli", Naples, Italy.
Giuliana GiannìPediatrics Department, Allergology and Immunology, Livorno Ospedali Riuniti, SIAIP Referent for Emilia-Romagna, Livorno, Italy.
Giovanni Cosimo IndirliPediatric Allergology and Immunology Society (SIAIP), Representative for Basilicata, Lecce, Italy.ORCID https://orcid.org/0009-0009-6389-5431
Enrica MancaPediatrics Department, Policlinico Riuniti, University Hospital of Foggia, Foggia, Italy.ORCID https://orcid.org/0000-0002-8723-0129
Filippo MondìDepartment of Maternal Infantile and Urological Science, Sapienza University of Rome, Roma, Italy.ORCID https://orcid.org/0009-0000-1880-0995
Valentina NosratianAllergy Center, IRCCS Istituto Giannina Gaslini, Genoa, Italy.ORCID https://orcid.org/0009-0001-7091-5981
Erica PendezzaAllergy Unit, Department of Pediatrics, Buzzi Children's Hospital, Milan, Italy.
Marco Ugo Andrea SartorioPediatric Allergology Unit, Department of Childhood and Developmental Medicine, "Fatebenefratelli-Sacco" Hospital, Milan, Italy.
Mauro CalvaniOperative Unit of Pediatrics, "S. Camillo-Forlanini" Hospital, Rome, Italy.ORCID https://orcid.org/0000-0001-7223-9692

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMilk ladder (ML) is considered a potential therapeutic option for managing cow's milk allergy (CMA). Although the ML was initially developed to reintroduce cow's milk into the diet for individuals with non-IgE mediated CMA, it has also recently been used in IgE-mediated CMA.

objectiveTo perform a systematic review and meta-analysis of the safety and efficacy of ML in children with IgE-mediated milk allergy.

methodsWe conducted a systematic literature review and meta-analysis of controlled studies in accordance with PRISMA guidelines. ML safety and ML efficacy compared to a strict avoidance diet and oral immunotherapy in children with IgE mediated CMA was evaluated. Meta-analysis was performed where ≥ 3 studies reported data. Methodological quality and risk of bias were systematically assessed.

resultsSix controlled studies (two randomized controlled trials and four observational controlled studies) met the inclusion criteria. ML resulted in the development of tolerance in 69% of participants (OR = 4.48; 95% CI = 2.51-8.00), with a significant improvement compared to the elimination diet. The meta-analysis of four studies showed that ML was 4.5 times more effective than a strict avoidance diet in inducing partial or total tolerance in ITT analysis and 8.4 times in PP analysis. Certainty of evidence was moderate, with low heterogeneity among studies. No significant difference in adverse events, severe systemic allergic reactions, and adrenaline use between the ML and avoidance diet groups were found. Only one study reported comparable efficacy between ML and oral immunotherapy with raw milk (OIT). No difference was found in the total number of mild to moderate adverse reactions between the groups (68.2% and 77.8, respectively; p = 0.44). The rates of epinephrine use at home were 14.3% and 11.8%, respectively, without significant difference between ML and OIT groups (p = 1).

conclusionsML represents a promising therapeutic approach for accelerating tolerance in children with IgE-mediated CMPA. Further research is needed to clarify milk ladder safety, as well as to identify predictive biomarkers for patient selection.

Indexed as

anaphylaxisbaked milk allergydesensitizationdietary therapyepinephrinemilk allergymilk ladderoral immunotherapytolerance

Identifiers

PMID41311241
PMCPMC12661123

What Socratic holds

Textmetadata
LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.