Karen Harris

Karen Harris is a professional writer and editor with more than two decades of experience in research-driven nonfiction writing. With a background in journalism and a Master's degree in English, she brings a meticulous approach to fact-finding, source evaluation, and clear communication of complex topics. Her work spans health, lifestyle, and consumer education, always with a focus on accuracy and readability.

Context

Hydrolyzed infant formulas (HF) contain partially or extensively broken-down milk proteins. They are frequently recommended for infants at elevated risk of allergic disease, particularly when breastfeeding is not possible.

Two main types exist:

  • Partially hydrolyzed formula (PHF)

  • Extensively hydrolyzed formula (EHF)

While hydrolyzed formulas are widely used in allergy prevention strategies, clinical evidence regarding their effectiveness compared with standard cow’s milk formula (CMF) or breast milk (BM) remains inconsistent.

This systematic review and meta-analysis evaluated whether early feeding with PHF or EHF influences the risk of allergic diseases in childhood.

Study Overview

Design
Systematic review and meta-analysis of clinical trials
PRISMA-guided
Registered at PROSPERO (CRD42022320787)


Data Sources
PubMed, Embase, Web of Science, Cochrane Library


Included Studies
24 trials
10,950 infants

17 trials included high-risk infants (family history of allergy)


Comparisons

  1. PHF vs CMF

  2. EHF vs CMF

  3. PHF vs BM

  4. EHF vs BM


Outcomes Assessed

  • Cow’s milk allergy

  • Eczema (atopic dermatitis)

  • Wheeze

  • Asthma

  • Allergic rhinitis

  • Food allergy

  • Sensitization

Outcomes were analyzed separately for children:

  • 0–2 years

  • 2 years


Evidence Grading
GRADE approach
Evidence ranged from low to moderate quality

Key Findings

1. Cow’s Milk Allergy (0–2 years)

Compared with CMF:

  • EHF reduced risk
    RR: 0.62
    95% CI: 0.39–0.99
    Evidence quality: Low

  • Evidence for PHF was insufficient for meta-analysis.

2. Eczema

Compared with CMF:

  • PHF reduced eczema risk in children <2 years
    RR: 0.71
    95% CI: 0.52–0.96
    Evidence quality: Moderate

  • EHF reduced eczema risk in children >2 years
    RR: 0.79
    95% CI: 0.67–0.94
    Evidence quality: Moderate

  • Age-specific differences were observed.

3. Wheeze

Compared with CMF:

  • PHF reduced wheeze risk at 0–2 years
    RR: 0.50
    95% CI: 0.29–0.85
    Evidence quality: Moderate

  • Compared with breast milk:

    • PHF increased wheeze risk
      RR: 1.61
      95% CI: 1.11–2.31

    • EHF increased wheeze risk
      RR: 1.64
      95% CI: 1.26–2.14


4. Other Allergic Outcomes

No consistent significant effects were observed for:

  • Asthma

  • Allergic rhinitis

  • Food allergy

  • Sensitization


Interpretation

Compared with standard cow’s milk formula:

  • EHF may reduce early cow’s milk allergy risk

  • PHF and EHF may reduce eczema risk

  • PHF may reduce early wheeze risk in high-risk infants

Compared with breast milk:

  • Both PHF and EHF were associated with increased wheeze risk

  • No consistent differences for other allergic outcomes

Most trials included high-risk infants.
Generalization to the general infant population is uncertain.

Overall evidence quality ranged from low to moderate.


Limitations

  • Many studies focused on high-risk infants

  • Variable diagnostic criteria across trials

  • Risk of bias in several included studies

  • Heterogeneity between interventions

  • Limited long-term follow-up beyond early childhood

Neutral Interpretation

Hydrolyzed formulas may provide selective preventive effects against certain allergic outcomes when compared with cow’s milk formula. However, compared with breast milk, no preventive advantage was demonstrated, and wheeze risk was higher.

The majority of available evidence applies to high-risk infants. Further high-quality trials in broader populations are required before general preventive recommendations can be supported.

Full Citation

Li X, He T, Duan S, Liang J, Feng G, Li F, Shen Z, Ye W, Liu B, Jiang B, Chen Y, Liu N, Szeto IMY, Cai L.
Infant formulas with partially or extensively hydrolyzed milk proteins for the prevention of allergic diseases: A systematic review and meta-analysis of clinical trials.
Advances in Nutrition. 2024.
PMID: 38579971
Available via PubMed: https://pubmed.ncbi.nlm.nih.gov/38579971/

Disclosure

This summary is based on the published systematic review and meta-analysis in Advances in Nutrition (2024).

It is provided for informational purposes only and does not constitute medical advice.

Breastfeeding is recommended where possible in accordance with international health authority guidelines.