Hydrolyzed Whey Formula Research Articles

Cost-effectiveness of therapeutic infant formulas for cow's milk protein allergy management.

Cow's milk protein allergy (CMPA) is children's most common food allergy. Therapeutic infant formulas for CMPA lead to symptom-free and potentially benefit early tolerance induction and reducing the allergic march in non-breastfed babies. This study assessed the cost-effectiveness of CMPA management with different therapeutic infant formulas in Thailand, which may reflect situations in developing countries throughout Asia. An analytic decision model was developed to simulate the occurrence of eczema, urticaria, asthma, rhinoconjunctivitis, or being symptom-free in infants with CMPA over 36 months. Extensively hydrolyzed casein formula with added probiotic Lacticaseibacillus rhamnosus (previously Lactobacillus rhamnosus) strain GG (EHCF+LGG), extensively hydrolyzed whey formula (EHWF), soy protein-based formula (SPF), and amino acid formula (AAF) were compared from the healthcare payer perspective. The results from a prospective cohort study were used for comparative effectiveness measures, while local experts were interviewed to estimate the healthcare resource used in the management of CMPA. The costs of healthcare resources were obtained from standard, publicly available sources. The direct medical cost of CMPA management was lowest for EHCF+LGG (USD 1,720), followed by SPF (USD 2,090), EHWF (USD 2,791), and AAF (USD 7,881). Compared with other formulas, EHCF+LGG was expected to save USD 370 (SPF), USD 1,071 (EHWF), and USD 6,161 (AAF) in the total cost of CMPA management over 36 months. In conclusion, EHCF+LGG was the most cost-effective strategy for managing non-breastfed infants with CMPA. This strategy was associated with more children developing immune tolerance to cow's milk and being symptom-free, contributing to overall cost-saving potential.

Cost-effectiveness of infant hypoallergenic formulas to manage cow’s milk protein allergy in France

ABSTRACT Background Clinician’s choice of hypoallergenic formulas in the first-line management of cow’s milk protein allergy (CMPA) should be informed by evidence on clinical efficacy and cost-effectiveness. Objective We compare the cost-effectiveness of amino acid-based formula (AAF), extensively hydrolyzed casein formula with Lactobacillus rhamnosus Gorbach Goldin (EHCF+LGG), extensively hydrolyzed whey formula (EHWF), and rice hydrolyzed formula (RHF) in non-breastfed children in France. Methods Immunotolerance and atopic manifestations’ prevalence were based on a prospective non-randomized study with a 36-month follow-up. Resource utilization was sourced from a survey of French clinicians, and unit costs were based on national data. Costs and health consequences were discounted at 2.5% annually. Results were reported using the Collective and French National Health Insurance perspectives. Results Children receiving EHCF+LGG were predicted to require less healthcare resources, given their reduced prevalence of CMPA symptoms at 3 years. In the base case, EHCF+LGG led to savings of at least €674 per child compared to AAF, EHWF, and RHF at 3 years, from both perspectives. Nutrition had the highest economic burden in CMPA, driven by hypoallergenic formulas and dietetic replacements costs. Results were robust to one-way and probabilistic sensitivity analyses. Conclusions EHCF+LGG was associated with more symptom-free time, higher immune tolerance, and lower costs.

Managing Cow's Milk Protein Allergy in Indonesia: A Cost-effectiveness Analysis of Hypoallergenic Milk Formulas from the Private Payers' Perspective.

Background: Cow’s milk protein allergy is very common in early childhood. Extensively hydrolyzed formulas are recommended in the first-line management of cow’s milk protein allergy in non-breastfed children. Choice of formulas should be informed by efficacy and cost data. Objectives: This study aims to compare the cost-effectiveness of extensively hydrolyzed casein formula with Lacticaseibacillus rhamnosus Gorbach Goldin (EHCF+LGG), extensively hydrolyzed whey formula (EHWF), amino acid formula, and soy formula in the first-line management of cow’s milk protein allergy in non-breastfed children in Indonesia. Methods: A trial-based decision analytic cohort model was adapted to simulate the occurrence of cow’s milk protein allergy symptoms or being symptom free. The model was based on a prospective nonrandomized study that followed up children for 36 months. Costs and health consequences were discounted at 3% annually. Resources required to manage cow’s milk protein allergy and unit costs for clinical appointments and exams were based on a panel of 15 clinicians, from a private payers’ perspective. Other unit costs were based on publicly available national data. Results were reported as cost per additional child free from allergic manifestations or per additional immunotolerant child at 3 years, and per life-years under the same conditions. Uncertainty was assessed using deterministic and probabilistic sensitivity analysis. Results: Children receiving EHCF+LGG were associated with more symptom-free time, a higher probability of cow’s milk tolerance at 3 years, and lower healthcare resources and transportation use when compared with children receiving other formulas (with 38%-49% lower costs). Formula costs were lower for soy, but EHCF+LGG was predicted to save 9% and 54% of overall costs compared with extensively hydrolyzed whey formula and amino acid formula, respectively. Results were robust to sensitivity analyses. Conclusion: Use of EHCF+LGG resulted in more symptom-free time and the highest 3-year probability of cow’s milk tolerance. It also led to healthcare resource and transportation savings when compared with other hypoallergenic milk formulas. Soy formula remained an alternative if formula price represents a major constraint.

Managing Cow’s Milk Protein Allergy in Indonesia: A Cost-effectiveness Analysis of Hypoallergenic Milk Formulas From the Private Payers’ Perspective

Background: Cow’s milk protein allergy is very common in early childhood. Extensively hydrolyzed formulas are recommended in the first-line management of cow’s milk protein allergy in non-breastfed children. Choice of formulas should be informed by efficacy and cost data. Objectives: This study aims to compare the cost-effectiveness of extensively hydrolyzed casein formula with Lacticaseibacillus rhamnosus Gorbach Goldin (EHCF+LGG), extensively hydrolyzed whey formula (EHWF), amino acid formula, and soy formula in the first-line management of cow’s milk protein allergy in non-breastfed children in Indonesia. Methods: A trial-based decision analytic cohort model was adapted to simulate the occurrence of cow’s milk protein allergy symptoms or being symptom free. The model was based on a prospective nonrandomized study that followed up children for 36 months. Costs and health consequences were discounted at 3% annually. Resources required to manage cow’s milk protein allergy and unit costs for clinical appointments and exams were based on a panel of 15 clinicians, from a private payers’ perspective. Other unit costs were based on publicly available national data. Results were reported as cost per additional child free from allergic manifestations or per additional immunotolerant child at 3 years, and per life-years under the same conditions. Uncertainty was assessed using deterministic and probabilistic sensitivity analysis. Results: Children receiving EHCF+LGG were associated with more symptom-free time, a higher probability of cow’s milk tolerance at 3 years, and lower healthcare resources and transportation use when compared with children receiving other formulas (with 38%-49% lower costs). Formula costs were lower for soy, but EHCF+LGG was predicted to save 9% and 54% of overall costs compared with extensively hydrolyzed whey formula and amino acid formula, respectively. Results were robust to sensitivity analyses. Conclusion: Use of EHCF+LGG resulted in more symptom-free time and the highest 3-year probability of cow’s milk tolerance. It also led to healthcare resource and transportation savings when compared with other hypoallergenic milk formulas. Soy formula remained an alternative if formula price represents a major constraint.

A partially hydrolyzed whey formula provides adequate nutrition in high-risk infants for allergy.

BACKGROUND/OBJECTIVESHydrolyzed formula is often fed to infants with gastrointestinal or immune issues, such as malabsorption or cow's milk allergy, because enzymatic treatment has rendered it more digestible and less allergenic than standard cow's milk formula (SF). Partially hydrolyzed formula (PHF) should be considered for those infants who are intolerant to extensively hydrolyzed formula. However, there are concerns about the nutritional insufficiencies of PHF. We aimed to evaluate the effects of PHF on the growth and health indicators in infants who were at high-risk of allergic disease and potential candidates for consuming PHF.SUBJECTS/METHODSA total of 83 infants aged 0–2 mon with a family history of allergies were assigned to consume either PHF or SF until 24 weeks of age. Anthropometric measures were obtained at baseline, 12 weeks, and 24 weeks; blood samples were drawn and evaluated at the end of the study.RESULTSNo significant differences were observed in weight, height, and weight-for-height at any time point in each sex between the PHF and SF groups. At 24 weeks of age, the weight-for-age and height-for-age z-scores of the SF group were higher than those of the PHF group, but there was no significant difference in the weight-for-height z-score. There were no significant differences in levels of white blood cells, hemoglobin, ferritin, protein, albumin, aspartate aminotransferase, alanine aminotransferase, eosinophil cationic protein, and immunoglobulin E.CONCLUSIONSIn this study, there were no differences in growth and blood panels between the infants consuming PHF or SF. Therefore, infants who are unable to tolerate SF can be fed PHF without nutritional concerns about growth.

Use of Thickeners Versus Hydrolysed Formulae in the Management of Gastro-oesophageal Reflux Disease in Infants: A Systematic Review

Background and objective: Regurgitation symptoms in many GERD infants might affect their nutrition status. This review compares thickeners and hydrolysis formula with cow’s milk in the evolution of regurgitation, weight and stool consistency changes in infants with GERD based on currently available evidence, as the benefits of using AR-F in infants with GERD is still contradictory. There is also evidence that hydrolysed formula plays a crucial role in regulating reflux. Methods: The search terms ‘thickener formula/pre-thickener’ OR ‘cow’s milk allergy/hydrolysis formula’ AND ‘gastro-oesophageal reflux disease (GERD)/regurgitations’ were used to search the electronic databases of NUsearch, Google Scholar, ScienceDirect and PubMed for randomised controlled trials (RCTs) published between 2005 and 2020 for thickened formula and 2010-2020 for hydrolysed formula that involved infants (Results: Seven eligible RCTs met the inclusion criteria. Thickened whey protein formula significantly reduced daily regurgitations by up to 7.7 episodes, while the results were insignificant in thickened or normal extensive hydrolysed casein milk (-4.2 vs -3, respectively). However, rice thickener significantly reduced regurgitation and weight gain by 1.261 kg in two months. An insignificant difference in stool consistency was found in most trials (P >0.05), except for the thickened casein formula as 64% of participants had normal stool density (P= 0.45). Conclusion: This study identified that using either thickening formula or extensively hydrolysed formula significantly reduced the number of regurgitations per day (mean range: -1.2 to -7.1; P<0.05). It does, however, seem that hydrolysed whey formula thickened with hydrolysed rice can support weight gain in failure to thrive infants.

Cost-effectiveness Analysis of Hypoallergenic Milk Formulas for the Management of Cow's Milk Protein Allergy in the United Kingdom.

Background: Cow’s milk protein allergy (CMPA) is the most common food allergy in early childhood. In most children CMPA resolves by age 5 or 6; however, if not treated correctly can provoke nutritional deficiency resulting in poor growth. Management consists of excluding cow’s milk from the diet, with hypoallergenic formulas (or non-dairy alternatives) being introduced to meet nutritional requirements.Objectives: To compare the cost-effectiveness of hypoallergenic formulas in reducing allergic manifestations and promoting immune tolerance in infants with immunoglobulin E (IgE)-mediated symptoms of CMPA.Methods: A trial-based decision analytic cohort model was developed to simulate the occurrence of urticaria, eczema, asthma, rhinoconjunctivitis, or being symptom-free in infants with CMPA in the United Kingdom. Amino acid-based formula (AAF), extensively hydrolysed casein formula containing Lactobacillus rhamnosus Gorbach Goldin (EHCF+LGG), extensively hydrolysed whey formula (EHWF), and soy formula (SF) were compared using the National Health Service (NHS) perspective, 3-year time horizon and 3.5% discount rate for cost and health consequences. Hypoallergenic formulas comparative efficacy was sourced from a prospective cohort study. Resources required to manage allergic symptoms were sourced from published literature, validated by a UK clinician, and applied to UK cost resources. Results were reported as cost per additional child free from allergic manifestations at 3 years and cost per additional immune tolerant child at 3 years.Results: In the base case, infants receiving EHCF+LGG were associated with lower NHS resource use and improved CMPA tolerance. Over the 3-year treatment period, savings of £119, £476, and £2645 were achieved with EHCF+LGG compared to SF, EHWF and AAF, respectively. Infant formula accounted for the largest proportion of resource consumption averaging 47% for all comparators, with a minimum of 31% for SF and a maximum of 69% for AAF over 3 years. General practitioners’ visits constituted the second highest cost component, approximately 16% of total costs across comparators. The results were robust to deterministic and probabilistic sensitivity analyses.Conclusions: Compared to AAF, SF, and EHWF hypoallergenic formulas, EHCF+LGG was the most cost-effective, associated with lower total costs and contributing to a higher proportion of children being symptom-free and developing immune tolerance 3-years after diagnosis.

Partially Hydrolyzed Whey Protein: A Review of Current Evidence, Implementation, and Further Directions

Background: Human milk is known to be the best nutrition for infants as it provides many health benefits. For non-breastfed infants, cow's milk based infant formula is the most optimal option to provide the needed nutrition. However, approximately 2-5% of all formula-fed infants experience cow’s milk allergy during their first year of life. Partially hydrolyzed whey formula (pHF-W) have been widely recommended to prevent the development of allergic disease in infants. However, according to epidemiological data, approximately half of the infants developing allergy are not part of the at-risk group.Objectives and Methods: This article aims to review the effects of pHF-W in preventing allergy, especially atopic disease, in all non-breastfed infants, as well as the safety aspect of pHF-W if used as routine formula. The role of pHF-W in the management of functional gastro-intestinal (GI) disorders is also reviewed.Results: Several clinical studies showed that pHF-W decrease the number of infants with eczema. The strongest evidence is provided by the 15-year follow up of the German Infant Nutritional Intervention study which showed reduction in the cumulative incidence of eczema and allergic rhinitis in pHF-W (OR 0.75, 95% CI 0.59-0.96 for eczema; OR 0.67, 95% CI 0.47-0.95 for allergic rhinitis) and casein extensively hydrolysed formula group (OR 0.60, 95% CI 0.46-0.77 for eczema; OR 0.59, 95% CI 0.41-0.84 for allergic rhinitis), compared to CMF as a control, after 15 years of follow-up. pHF-W was also found to be beneficial in the management of functional GI disorders such as regurgitation, constipation and colic.Conclusions: The use of pHF-W in allergic infants has been recommended in various guidelines across the countries, as a primary prevention of allergic disease. One pHF-W has been approved by the US FDA and the European Commission's European Food Safety Authority (EFSA) for its safety and suitability as a routine infant formula for all healthy infants. According to the data obtained in the management of functional GI disorders, pHF-W is better tolerated than formula with intact protein. Further studies assessing the effect of routine use of pHF-W in a larger population of non-breastfed infants should also be conducted, in order to observe any potential harm and to determine the benefit and cost-effectiveness ratio.

The Impact of Formula Choice for the Management of Pediatric Cow’s Milk Allergy on the Occurrence of Other Allergic Manifestations: The Atopic March Cohort Study

To compare the impact of different formulas on the occurrence of other atopic manifestations and the time of immune tolerance acquisition. In a 36-month prospective cohort study, the occurrence of other atopic manifestations (eczema, urticaria, asthma, and rhinoconjunctivitis) and the time of immune tolerance acquisition were comparatively evaluated in immunoglobulin E-mediated children with cow's milk allergy (CMA) treated with extensively hydrolyzed casein formula containing the probiotic L. rhamnosus GG (EHCF+LGG), rice hydrolyzed formula, soy formula, extensively hydrolyzed whey formula (EHWF), or amino acid-based formula. In total, 365 subjects were enrolled into the study, 73 per formula cohort. The incidence of atopic manifestations was 0.22 (Bonferroni-corrected 95% CI 0.09-0.34) in the EHCF+LGG cohort; 0.52 (0.37-0.67) in the rice hydrolyzed formula cohort; 0.58 (0.43-0.72) in the soy formula cohort; 0.51 (0.36-0.66) in the EHWF cohort; and 0.77 (0.64-0.89) in the amino acid-based formula cohort. The incidence of atopic manifestations in the rice hydrolyzed formula, soy formula, EHWF, and amino acid-based formula cohorts vs the EHCF+LGG cohort was always greater than the prespecified absolute difference of 0.25 at an alpha-level of 0.0125, with corresponding risk ratios of 2.37 (1.46-3.86, P<.001) for rice hydrolyzed formula vs EHCF+LGG; 2.62 (1.63-4.22, P<.001) for soy formula vs EHCF+LGG; 2.31 (1.42-3.77, P<.001) for EHWF vs EHCF+LGG; and 3.50 (2.23-5.49, P<.001) for amino acid-based formula vs EHCF+LGG. The 36-month immune tolerance acquisition rate was greater in the EHCF+LGG cohort. The use of EHCF+LGG for CMA treatment is associated with lower incidence of atopic manifestations and greater rate of immune tolerance acquisition.

Effectiveness of using an extensively hydrolyzed casein formula supplemented with Lactobacillus rhamnosus GG compared with an extensively hydrolysed whey formula in managing cow’s milk protein allergic infants

Aim: To assess the comparative effectiveness of two hypoallergenic formulae in managing cow's milk allergic infants. Materials & methods: This study retrospectively analyzed the case records of 940 formula-fed cow's milk allergic infants in the UK extracted from The Health Improvement Network database. Results: At 24 months after starting a formula, 77% of infants fed an extensively hydrolyzed casein formula supplemented with Lactobacillus rhamnosus GG (eHCF LGG;n=470) were estimated to have been successfully managed compared with 63% of matched infants who were fed an extensively hydrolyzed whey formula (eHWF;n=470;p < 0.001). Additionally, significantly more eHWF-fed infants were estimated to be experiencing gastrointestinal symptoms, eczema and asthma (7.1 vs 3.1%; p < 0.02) at 24 months. Conclusion: First-line management of newly diagnosed cow's milk allergic infants with eHCF LGG may slow down the allergic march seen in cow's milk allergic children.

Partially Hydrolysed Whey-Based Formulae with Reduced Protein Content Support Adequate Infant Growth and Are Well Tolerated: Results of a Randomised Controlled Trial in Healthy Term Infants.

The current study aimed to investigate growth, safety and tolerance of partially hydrolysed infant formulae in healthy full-term infants. Fully formula-fed infants were randomised ≤14 days of age to receive a partially hydrolysed whey formula with 2.27 g protein/100 kcal (pHF2.27) or the same formula with 1.8 g or 2.0 g protein/100 kcal (pHF1.8 and pHF2.0) until 4 months of age. The primary outcome was equivalence in daily weight gain within margins of ± 3 g/day; comparison with WHO Child Growth Standards; gastrointestinal tolerance parameters and number of (serious) adverse events were secondary outcomes. A total of 207 infants were randomised, and 61 (pHF1.8), 46 (pHF2.0) and 48 (pHF2.27) infants completed the study per protocol. Equivalence in daily weight gain was demonstrated for the comparison of pHF1.8 and pHF2.27, i.e., the estimated difference was −1.12 g/day (90% CI: [−2.72; 0.47]) but was inconclusive for the comparisons of pHF2.0 and pHF2.27 with a difference of −2.52 g/day (90% CI: [−4.23; −0.81]). All groups showed adequate infant growth in comparison with the World Health Organization (WHO) Child Growth Standards. To conclude, the evaluated partially hydrolysed formulae varying in protein content support adequate growth and are safe and well tolerated in healthy infants.

Evaluation of the efficiency of hydrolyzed whey formula to prevent cow's milk allergy in the BALB/c mouse model.

Partially hydrolyzed milk formulas have been proposed for primary prevention in at-risk infants, but evidence of their efficiency and elucidation of the underlying mechanisms are still lacking. Thanks to a Th2-biased mouse model mimicking at-risk patients, we aimed to assess the potency of a partially hydrolyzed whey formula (pHWF) to induce oral tolerance thus preventing further cow's milk (CM) allergy. BALB/c mice were gavaged with pHWF, standard milk formula (SF), or vehicle only (PBS+). All mice were then orally sensitized to CM using cholera toxin and further chronically exposed to CM. Humoral (IgE, IgG1, IgG2a) and cellular (Th2/Th1/Th17 cytokine secretion; frequency of CD4+GATA3+ and CD4+CD25+Foxp3+ T cells in the spleen) responses against β-lactoglobulin (BLG) and whole caseins (CAS) were assessed, as well as a marker of elicitation of allergic reaction (mMCP-1) released after an oral challenge with CM. All markers of sensitization and of allergic reaction were evidenced in the PBS+ mice and were significantly enhanced upon chronic exposure. Gavage with SF totally and durably prevented sensitization and elicitation of the allergic reaction. Conversely, pre-treatment with pHWF only reduced BLG-specific sensitization (IgE, Th2 cytokines), with no significant effect on sensitization to caseins. However, pHWF pre-treatment significantly reduced mMCP-1 concentration in plasma after CM challenges. CD4+CD25+Foxp3+ Treg cell frequency could not be correlated with tolerance efficiency. Partially hydrolyzed whey formula only partially prevents the further development of CM allergy in this Th2-biased model. A hydrolysate from both whey and casein fractions may be more efficient.

A perspective on partially hydrolyzed protein infant formula in nonexclusively breastfed infants.

The World Health Organization recommends that infants should be exclusively breastfed for the first 6 months of life to provide optimal nutrition in this critical period of life. After this, infants should receive nutritionally adequate and safe complementary foods while breastfeeding continues for up to 2 years of age or beyond. For nonbreastfed infants, infant formula is an available option to provide the nutrition needed. Infant formula is usually prepared from industrially modified cow’s milk and processed to adjust for the nutritional needs of infants. However, cow’s milk is one of the most common causes of food allergy, affecting 2%–5% of all formula-fed infants during their first year of life. One strategy to prevent cow’s milk allergy in nonbreastfed infants is the use of partially hydrolyzed formula (pHF) in high-risk infants, which are infants born in families with atopic disease. However, based on an epidemiological study, approximately half of the infants who develop allergy are not part of the at-risk group. This is because the non-at-risk group is significantly larger than the at-risk group and the non-at-risk infants have approximately 15% risk of developing allergies. This study aimed to evaluate the effects of partially hydrolyzed whey formula (pHF-W) in nonbreastfed infants and determine whether pHF-W can prevent atopic disease in high-risk infants and can be used as routine starter formula regardless of the allergy risk status.

A Pooled Analysis of Growth and Tolerance of Infants Exclusively Fed Partially Hydrolyzed Whey or Intact Protein-Based Infant Formulas.

Background For infants who are partially or exclusively fed infant formula, many options exist with compositional differences between formulas making choices difficult for caregivers and healthcare professionals. The protein in routine infant formulas differs by the source, fraction of cow's milk protein used, and degree of hydrolysis. All commercially available regulated infant formulas support growth and development, but different stool patterns have been observed based on formula composition. A pooled analysis of seven clinical trials was conducted to examine growth, stool consistency, and stool frequency of infants fed an intact cow's milk-based formula (CMF) or a partially hydrolyzed whey formula (PHF-W) from a single manufacturer. Methods. Individual subject data from seven infant formula growth studies (3 CMF, 4 PHF-W) were pooled and analyzed. All studies included healthy, full-term, formula-fed infants enrolled at 14 days of age with outcomes assessed over 4 months. Gains in weight and length to 4 months were analyzed using linear regression accounting for clustering within study. Outcomes of caregiver-reported stool consistency and frequency were analyzed using a longitudinal multinomial model. Results Data from 511 infants were included (197 CMF, 314 PHF-W). There were no differences in weight gain between groups. There was no difference in length gain in girls fed PHF-W while boys fed PHF-W had a significant difference of +0.016 cm/month compared to boys fed CMF. Infants fed PHF-W had a significantly higher probability of soft and lower probability of hard stools as compared to infants fed CMF at each time point (p<0.001). Stool frequency was similar between groups. Conclusions Infants fed CMF and PHF-W exhibit appropriate growth with comparable gains in weight and length through 4 months. More soft and fewer hard stools are observed in infants fed PHF-W compared to CMF. This difference could help to inform decision-making when choosing an infant formula.

The influence of breastfeeding in breast-fed infants with atopic dermatitis.

The aim of this study was to evaluate whether breastfeeding should be discontinued for exclusively breast-fed infants with atopic dermatitis (AD). Eighty-seven exclusively breast-fed infants with AD were enrolled in a prospective observational study. The infants were divided into 3 groups: breastfeeding only (BM group), partial breastfeeding and partial partially hydrolyzed whey formula (pHF-W) (Partial group) and pHF-W only (DC group). The extent and severity of AD were evaluated with the Patient-Oriented SCORing Atopic Dermatitis (PO-SCORAD) index at enrollment and 3 and 6 months later. There were no significant differences in parental atopy history, PO-SCORAD scores, and medication scores at baseline. At month 3 and 6, the PO-SCORAD scores were significantly decreased in all groups. PO-SCORAD scores at month 3 and 6 and at the last time point when topical corticosteroids were given were significantly different among the groups. Stepwise multiple linear regression analysis showed that baseline PO-SCORAD scores and stopping breastfeeding were significantly associated with month 3 PO-SCORAD scores (p<0.001), after adjusting for sex, age, baseline medication scores, partial breastfeeding and parental atopy history. In addition to baseline PO-SCORAD scores and stopping breastfeeding, partial breastfeeding was significantly associated with month 6 PO-SCORAD scores. Long-term follow-up showed that only stopping breastfeeding was significantly associated with the last time point when topical corticosteroids were given (p=0.014). For exclusively breast-fed infants with AD, discontinuing breastfeeding and shifting to pHF-W might help to improve symptoms and shorten the duration of AD regardless of sex, age and parental atopy history.

WITHDRAWN: Infant formulas containing hydrolysed protein for prevention of allergic disease and food allergy.

Allergy is common and may be associated with foods, including cow's milk formula (CMF). Formulas containing hydrolysed proteins have been used to treat infants with allergy. However, it is unclear whether hydrolysed formulas can be advocated for prevention of allergy in infants. To compare effects on allergy and food allergy when infants are fed a hydrolysed formula versus CMF or human breast milk. If hydrolysed formulas are effective, to determine what type of hydrolysed formula is most effective, including extensively or partially hydrolysed formula (EHF/PHF). To determine which infants at low or high risk of allergy and which infants receiving early, short-term or prolonged formula feeding may benefit from hydrolysed formulas. We used the standard search strategy of the Cochrane Neonatal Review Group supplemented by cross referencing of previous reviews and publications (updated August 2016). We searched for randomised and quasi-randomised trials that compared use of a hydrolysed formula versus human milk or CMF. Trials with ≥ 80% follow-up of participants were eligible for inclusion. We independently assessed eligibility of studies for inclusion, methodological quality and data extraction. Primary outcomes included clinical allergy, specific allergy and food allergy. We conducted meta-analysis using a fixed-effect (FE) model. Two studies assessed the effect of three to four days' infant supplementation with an EHF whilst in hospital after birth versus pasteurised human milk feed. Results showed no difference in infant allergy or childhood cow's milk allergy (CMA). No eligible trials compared prolonged hydrolysed formula versus human milk feeding.Two studies assessed the effect of three to four days infant supplementation with an EHF versus a CMF. One large quasi-random study reported a reduction in infant CMA of borderline significance among low-risk infants (risk ratio (RR) 0.62, 95% confidence interval (CI) 0.38 to 1.00).Prolonged infant feeding with a hydrolysed formula compared with a CMF was associated with a reduction in infant allergy (eight studies, 2852 infants; FE RR 0.82, 95% CI 0.72 to 0.95; risk difference (RD) -0.04, 95% CI -0.08 to -0.01; number needed to treat for an additional beneficial outcome (NNTB) 25, 95% CI 12.5 to 100) and infant CMA (two studies, 405 infants; FE RR 0.38, 95% CI 0.16 to 0.86). We had substantial methodological concerns regarding studies and concerns regarding publication bias, as substantial numbers of studies including those in high-risk infants have not comprehensively reported allergy outcomes (GRADE quality of evidence 'very low').Prolonged infant feeding with a hydrolysed formula compared with a CMF was not associated with a difference in childhood allergy and led to no differences in specific allergy, including infant and childhood asthma, eczema and rhinitis and infant food allergy. Many of the analyses assessing specific allergy are underpowered.Subroup analyses showed that infant allergy was reduced in studies that enrolled infants at high risk of allergy who used a hydrolysed formula compared with a CMF; used a PHF compared with a CMF; used prolonged and exclusive feeding of a hydrolysed formula compared with a CMF; and used a partially hydrolysed whey formula compared with a CMF. Studies that enrolled infants at high risk of allergy; used a PHF compared with a CMF; used prolonged and exclusive feeding of a hydrolysed formula compared with a CMF; and used a partially hydrolysed whey formula compared with a CMF found a reduction in infant CMA. We found no evidence to support short-term or prolonged feeding with a hydrolysed formula compared with exclusive breast feeding for prevention of allergy. Very low-quality evidence indicates that short-term use of an EHF compared with a CMF may prevent infant CMA.In infants at high risk of allergy not exclusively breast fed, very low-quality evidence suggests that prolonged hydrolysed formula feeding compared with CMF feeding reduces infant allergy and infant CMA. Studies have found no difference in childhood allergy and no difference in specific allergy, including infant and childhood asthma, eczema and rhinitis and infant food allergy.Very low-quality evidence shows that prolonged use of a partially hydrolysed formula compared with a CMF for partial or exclusive feeding was associated with a reduction in infant allergy incidence and CMA incidence, and that prolonged use of an EHF versus a PHF reduces infant food allergy.

Infant formulas containing hydrolysed protein for prevention of allergic disease and food allergy.

Allergy is common and may be associated with foods, including cow's milk formula (CMF). Formulas containing hydrolysed proteins have been used to treat infants with allergy. However, it is unclear whether hydrolysed formulas can be advocated for prevention of allergy in infants. To compare effects on allergy and food allergy when infants are fed a hydrolysed formula versus CMF or human breast milk. If hydrolysed formulas are effective, to determine what type of hydrolysed formula is most effective, including extensively or partially hydrolysed formula (EHF/PHF). To determine which infants at low or high risk of allergy and which infants receiving early, short-term or prolonged formula feeding may benefit from hydrolysed formulas. We used the standard search strategy of the Cochrane Neonatal Review Group supplemented by cross referencing of previous reviews and publications (updated August 2016). We searched for randomised and quasi-randomised trials that compared use of a hydrolysed formula versus human milk or CMF. Trials with ≥ 80% follow-up of participants were eligible for inclusion. We independently assessed eligibility of studies for inclusion, methodological quality and data extraction. Primary outcomes included clinical allergy, specific allergy and food allergy. We conducted meta-analysis using a fixed-effect (FE) model. Two studies assessed the effect of three to four days' infant supplementation with an EHF whilst in hospital after birth versus pasteurised human milk feed. Results showed no difference in infant allergy or childhood cow's milk allergy (CMA). No eligible trials compared prolonged hydrolysed formula versus human milk feeding.Two studies assessed the effect of three to four days' infant supplementation with an EHF versus a CMF. One large quasi-random study reported a reduction in infant CMA of borderline significance among low-risk infants (risk ratio (RR) 0.62, 95% confidence interval (CI) 0.38 to 1.00).Prolonged infant feeding with a hydrolysed formula compared with a CMF was associated with a reduction in infant allergy (eight studies, 2852 infants; FE RR 0.82, 95% CI 0.72 to 0.95; risk difference (RD) -0.04, 95% CI -0.08 to -0.01; number needed to treat for an additional beneficial outcome (NNTB) 25, 95% CI 12.5 to 100) and infant CMA (two studies, 405 infants; FE RR 0.38, 95% CI 0.16 to 0.86). We had substantial methodological concerns regarding studies and concerns regarding publication bias, as substantial numbers of studies including those in high-risk infants have not comprehensively reported allergy outcomes (GRADE quality of evidence 'very low').Prolonged infant feeding with a hydrolysed formula compared with a CMF was not associated with a difference in childhood allergy and led to no differences in specific allergy, including infant and childhood asthma, eczema and rhinitis and infant food allergy. Many of the analyses assessing specific allergy are underpowered.Subroup analyses showed that infant allergy was reduced in studies that enrolled infants at high risk of allergy who used a hydrolysed formula compared with a CMF; used a PHF compared with a CMF; used prolonged and exclusive feeding of a hydrolysed formula compared with a CMF; and used a partially hydrolysed whey formula compared with a CMF. Studies that enrolled infants at high risk of allergy; used a PHF compared with a CMF; used prolonged and exclusive feeding of a hydrolysed formula compared with a CMF; and used a partially hydrolysed whey formula compared with a CMF found a reduction in infant CMA. We found no evidence to support short-term or prolonged feeding with a hydrolysed formula compared with exclusive breast feeding for prevention of allergy. Very low-quality evidence indicates that short-term use of an EHF compared with a CMF may prevent infant CMA.In infants at high risk of allergy not exclusively breast fed, very low-quality evidence suggests that prolonged hydrolysed formula feeding compared with CMF feeding reduces infant allergy and infant CMA. Studies have found no difference in childhood allergy and no difference in specific allergy, including infant and childhood asthma, eczema and rhinitis and infant food allergy.Very low-quality evidence shows that prolonged use of a partially hydrolysed formula compared with a CMF for partial or exclusive feeding was associated with a reduction in infant allergy incidence and CMA incidence, and that prolonged use of an EHF versus a PHF reduces infant food allergy.

Tolerance of Partially Hydrolyzed Whey Formula in Cow's Milk Allergic Patients

Tolerance of Partially Hydrolyzed Whey Formula in Cow's Milk Allergic Patients

Five-Year Follow-Up of High-Risk Infants with Family History of Allergy Who Were Exclusively Breast-Fed or Fed Partial Whey Hydrolysate, Soy, and Conventional Cow's Milk Formulas: Expression of Serious Concern.

Five-Year Follow-Up of High-Risk Infants with Family History of Allergy Who Were Exclusively Breast-Fed or Fed Partial Whey Hydrolysate, Soy, and Conventional Cow's Milk Formulas: Expression of Serious Concern.

Preventive effect of prenatal education and partially hydrolyzed whey formula on infantile allergy: a prospective study

Objective To explore the preventive effect of prenatal education and partially hydrolyzed whey formula (pHF-W) on infantile allergy. Methods We conducted a prospective study of 1 773 term and healthy infants born in five hospitals in Guangdong Province from November 2011 to November 2013. According to different feeding methods within four months after birth, they were divided into pHF-W group (653 cases), cow's milk formula (CMF) group (246 cases) and exclusive breast-feeding group (874 cases). We publicise maternal education during pregnancy, and inform the importance of balanced nutrition, and dietary structure. All infants and their mothers were followed up for 12 months. The incidences of food allergies, physical growth parameters were analyzed. Umbilical cord blood total IgE and serum total IgE at three and six months after birth were tested. Analysis of variance, Kruskal-Wallis test, Chi-square test or the Bonferroni tests were used for statistical analysis. Results Among the 1 773 infants, there were 893 males (50.4%), and 542 (30.6%) were born by cesarean section. The average birth age was (39.0±0.7) gestational weeks. Demographic characteristics among the three groups had no statistically significant difference (all P>0.05). The overall incidence of allergy in the 1 773 cases was 29.7% (526/1 773), and the onset of allergy was three to eight months after birth, with an average of (6.2±1.5) months. The incidences of skin symptoms, gastrointestinal symptoms and respiratory symptoms were 28.2% (500/1 773), 1.1% (20/1 773) and 0.3% (6/1 773), respectively. Foods of infant allergy were eggs (35.0%, 7/20), milk (30.0%, 6/20), fish and shrimp (15.0%, 3/20), peanut (10.0%, 2/20) and legumes (10.0%, 2/20). Incidences of allergic manifestation and atopic dermatitis in pHF-W group[28.6%(187/653) and 27.3%(178/653)]and breast-feeding group[28.4% (248/874) and 27.0%(236/874)] was lower than that in CMF group [(37.0%(91/246) and 35.0%(35/246), χ2=7.356 and 6.456, all P 0.05). Conclusion Prenatal education and partially hydrolyzed whey formula reduces the incidence of allergic disease in infants. Key words: Hypersensitivity; Lactalbumin; Infant formula; Pregnant women; Early medical intervention; Health Education; Prospective studies