Mixed results for hydrolysed milk formulas in allergy prevention among children – meta-analysis
The meta-analysis of clinical trials compared the effects of hydrolysed milk formulas with cow's milk and breast milk on allergies in infants and toddlers. The results showed that hydrolysed milk formula may reduce the risk of certain allergies compared to cow’s milk but increase the risk of wheeze compared to breast milk.
The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to grade the strength of evidence.
“GRADE was low for the evidence that, compared with cow’s milk formula (CMF), infants early fed with extensively hydrolysed formula had lower risk of cow's milk allergy at age 0–2 years. Moderate evidence supported that partially hydrolysed formula (PHF) and extensively hydrolysed formula (EHF) reduced risk of eczema in children aged younger or older than 2 years of age, respectively. We also identified moderate systematic evidence indicating that PHF reduced risk of wheeze at age 0–2 years compared with CMF, but PHF and EHF increased the risk compared with breast milk (BM). Neither PHF nor EHF had significant effects on other allergic diseases in children of any age,” wrote the researchers in Advances in Nutrition.
Early nutrition affects children’s risk of developing allergic diseases, and newborn feeding practices have significant impact on early childhood nutrition. Early childhood feeding is therefore an important target for tailored interventions to prevent allergies.
For infants with cow's milk allergy, hydrolysed milk formula (HF) is recommended as a form of treatment and management. Put simply, HF contains milk proteins that have already been broken down into smaller compounds that are easier to digest, lessening sensitivity and reducing the likelihood of allergic reactions. PHF and EHF are the two types of HFs that vary in the extent of protein hydrolysis.
Despite the widely recommended usage of PHF or EHF for preventing allergies, clinical studies have been inconclusive regarding their efficacy compared with that of cow's milk formula or breast milk. Therefore, researchers wanted to evaluate the effects of PHF or EHF compared with those of CMF or BM on managing allergies among children. The allergies studied include cow's milk allergy, allergic rhinitis, eczema, asthma, wheeze, food allergy, and sensitisation (the process of developing sensitivity towards a certain allergen).
The study
Researchers pulled data from PubMed, Embase, Cochrane Library, and Web of Science for clinical trials published from inception to 21 October 2022. All meta-analyses were conducted for different types of allergic diseases in children aged younger or older than 2 years old.
Overall, 24 trials were included, 17 of which included high-risk infants. There were 10,950 infants altogether.
The duration of the trials ranged from 2 weeks to 8 months, and the results were determined when the study subjects were between 1 month and 15 years of age. The included studies were randomised controlled trials (RCTs) and quasi-RCTs, as well as controlled clinical trials.
The study subjects were given PHF or EHF, including partially hydrolysed whey (PHF-W) or partially hydrolysed casein (PHF-C) formulas and extensively hydrolysed whey (EHF-W) or extensively hydrolysed casein (EHF-C) formulas. To compare the effects of PHF and EHF compared to CMF and BM, the trials included control groups that were provided with either CMF or BM.
The researchers then analysed the effects of PHF, EHF, CMF, and BM on allergies that included cow's milk allergy, atopic dermatitis/eczema, allergic rhinitis, asthma, wheeze, food allergy, or sensitisation.
About 70% of participants showed favourable effects of HF on allergies in children younger than 2 years old, and 66% of participants showed favourable effects of HF on allergies in children older than 2 years old.
The results showed that neither EHF-W nor EHF-C increased risk of eczema and sensitisation. Additionally, they also found that compared to BM, EHF and PHF increased risk of wheeze.
“Our results showed low-quality evidence that EHF contributed to lower risk of cow's milk allergy than CMF in children aged less than 2 years. GRADE indicated moderate evidence that compared with CMF, feeding with PHF reduced risk of eczema in children aged less than 2 years and EHF decreased risk of eczema after the age of 2 years. We also identified moderate systematic evidence indicating that PHF instead of CMF reduced risk of wheeze at age 0–2 years. However, there was low or moderate evidence suggesting that compared with BM, neither PHF nor EHF increased risk of allergic diseases in children aged less than 2 years, except for wheeze. No significant effects of HF on other allergic diseases were observed in children of any age,” said the researchers.
Implications and future research
In line with the researchers’ findings, previous guidelines have recommended using EHF for managing infants with cow’s milk allergy and preventing allergic diseases. Several studies have also advocated using PHF or EHF to prevent eczema in high-risk infants and children.
“It is biologically plausible that EHF prevents cow's milk allergy. CMF consists of at least 25 different milk proteins, all of which have the potential to act as allergens. Among these, the major allergenic proteins, casein, β-lactoglobulin, and α-lactalbumin contain multiple sensitisation epitopes,” said the researchers.
Owing to a lower degree of hydrolysis and a higher amount of residual antigenic determinants, PHF may be less effective than EHF in preventing cow's milk allergy.
“We found evidence that early feeding EHF in replacement of CMF may reduce risk of cow's milk allergy. Early feeding PHF or EHF may decrease risk of eczema. Moreover, PHF may lessen risk of wheeze in high-risk infants compared with that by CMF but PHF and EHF may increase risk of wheeze but no other allergic diseases compared with that by BM. Given that the majority of studies included high-risk infants, more research on non–high-risk infants is advised before the implementation of this practice,” said the researchers.
“Future studies comparing PHF or EHF with CMF should provide detailed information on the sources of hydrolysed proteins. Moreover, previous research elucidated that the preventive efficacy of HF was influenced by multiple factors, including the degree of hydrolysis, the source of hydrolysed proteins, and the method of hydrolysis. To shine light on the effect of HF, future investigations should strive to encompass not only the degree of hydrolysis but also different hydrolysis methods,” they concluded.
Source: Advances in Nutrition
DOI: https://doi.org/10.1016/j.advnut.2024.100217
“Infant Formulas With Partially or Extensively Hydrolyzed Milk Proteins for the Prevention of Allergic Diseases: A Systematic Review and Meta-Analysis of Clinical Trials”
Authors: Xiaoxu Li, Tingchao He et al.
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