Hydrolyzed Infant Formula Research Articles

Partially hydrolyzed 100% whey protein infant formula and atopic dermatitis risk reduction: a systematic review of the literature

The incidence of atopic dermatitis (AD) is increasing worldwide. Clinical studies have observed reduced risks of AD among infants fed with 100% whey partially hydrolyzed infant formula (PHF-W) compared with intact protein cow's milk formula. To evaluate this potential relationship more comprehensively, a systematic review of the literature was conducted. Studies (n = 18, representing 12 distinct study populations) that specified the protein source of the formula, evaluated healthy-term infants, compared the use of PHF-W with intact protein cow's milk formula, and reported results for AD were included. A critical assessment of the methodological quality of studies was conducted. In all studies, a reduced incidence of AD and/or atopic manifestations that included AD was observed. The cumulative incidence of AD was significantly lower among infants over at least 3 years of follow-up in the PHF-W group compared with the intact protein cow's milk group. Exclusive breastfeeding should be encouraged as the primary means to prevent atopic risk. However, when infants are not exclusively breastfed, PHF-W may be considered an effective measure to potentially reduce the risk of developing AD.

Impact of early feeding on childhood eczema: development after nutritional intervention compared with the natural course – the GINIplus study up to the age of 6 years

Nutritional intervention with hydrolysed infant formulas has been shown efficacious in preventing eczema in children predisposed to allergy. However, this preventive effect has never been related to the natural course of eczema in children with or without a family history of allergy. The aim of this study therefore was to compare the course of eczema in predisposed children after nutritional intervention to the natural course of eczema. The prospective German birth cohort study GINIplus includes a total of 5991 children, subdivided into interventional and non-interventional groups. Children with a familial predisposition for allergy whose parents agreed to participate in the prospective, double-blind intervention trial (N=2252) were randomly assigned at birth to one of four formulas: partially or extensively hydrolysed whey, extensively hydrolysed casein (eHF-C) or standard cow's milk formula. Children with or without familial predisposition represented the non-interventional group (N=3739). Follow-up data were taken from yearly self-administered questionnaires from 1 up to 6 years. The outcome was physician-diagnosed eczema and its symptoms. The cumulative incidence of eczema in predisposed children with or without nutritional intervention was compared with that of non-predisposed children who did not receive intervention. Cox regression was used to adjust for confounding. Predisposed children without nutritional intervention had a 2.1 times higher risk for eczema [95% confidence interval (CI) 1.6-2.7] than children without a familial predisposition. The risk was smaller with nutritional intervention even levelling out to 1.3 (95% CI 0.9-1.9) in children fed eHF-C formula. Although direct comparability is somewhat restricted, the data demonstrate that early intervention with hydrolysed infant formulas can substantially compensate up until the age of 6 years for an enhanced risk of childhood eczema due to familial predisposition to allergy.

Primary prevention with hydrolysed formula: does it change natural onset of allergic disease?

Cite this as: J. Sinn and D. A. Osborn, Clinical & Experimental Allergy, 2010 (40) 534–535. There is some evidence to support the use of infant dietary interventions for prevention of allergy, particularly eczema in infants. Several Cochrane Systematic Reviews [1–4] have examined evidence for use of various interventions and reported that use of a partially hydrolysed or extensively hydrolysed infant formula may prevent allergy in infancy. There is no evidence of benefit from use of a soy formula [1] and inadequate evidence to date to determine the allergy preventing effects of probiotics and prebiotics [3, 4] added to infant feeds. Evidence of benefit from use of a hydrolysed formula is largely restricted to infants at high risk based on family history [2]. Several meta-analyses of observational studies [5, 6] and a cluster randomized trial of breastfeeding support measures [7] provide some evidence that exclusive breastfeeding may be effective in preventing infant eczema as well as gastrointestinal infections. Based on current evidence, several societies [8, 9] have recommended allergy prevention policies that include use of a partially hydrolysed formula if there is inadequate breast milk for infants with a positive family history of allergy. In this issue, the GINIplus study is reported with outcomes up to 6 years of age [10]. In the original GINI study [11], 2252 infants at high risk of allergy based on a first-degree family history of allergy were randomized to one of the four study formulas – a cow's milk formula, a partially hydrolysed whey formula, an extensively hydrolysed whey and an extensively hydrolysed casein formula. In intention-to-treat analyses, several publications of the GINI study [11–13] with follow-up to 6 years have reported a significant reduction in infant eczema in infants fed an extensively hydrolysed casein but not the other types of hydrolysed formula compared with use of a cow's milk formula. However, these results should be viewed in the context of all the evidence. The Cochrane review [2] reported methodological concerns with almost all studies, with the GINI study reporting between 10% and 20% losses to follow-up at various time-points. The overall meta-analyses found a significant reduction in infant allergy from use of a hydrolysed formula, with some evidence of benefit from both an extensively hydrolysed for prevention of eczema and a partially hydrolysed formula for prevention of all allergy although there is some heterogeneity in meta-analysis findings. The report in this issue is rather complex [10], reporting a modified intention to treat analysis of the GINIplus study. It includes infants at high risk of allergy randomized to different formulas, but also those infants not randomized. The non-randomized infants include groups that were low risk, therefore not eligible for randomization, as well as non-randomized high-risk infants. To complicate the report further, randomized high-risk infants who were non-compliant with treatment are reported separately. There is an attempt to adjust for non-comparable groups by using regression techniques. Dropout rates averaged 23%. Given the modified intention-to-treat analysis, for which there is empirical evidence for bias from this practice [14], it is difficult to determine if much can be concluded from the results of this complicated analysis. However, in brief, the authors report that the findings largely confirm the findings of their other reports. High-risk infants are more likely to develop allergy than low-risk infants, and only the intervention group fed an extensively hydrolysed casein formula were not at significantly increased risk of allergy diagnosis or symptoms compared with the low-risk non-intervention group. High-risk infants fed partially or extensively hydrolysed whey based formulas or a cow's milk formulas were still at significantly increased risk of allergy. Of interest is that the non-compliant group were also at significantly increased risk. We will never know whether this is due to their lack of compliance or whether non-compliance was related to allergy symptoms. However, excluding this group from an intention to treat analysis has created the potential for bias [14]. The GINIplus study provides intriguing evidence that should guide the choice of hydrolysed formula type for future studies. The Cochrane review [2] reinforces this and concludes that in view of methodological concerns and inconsistency of findings, further large, well-designed trials comparing formulas containing partially hydrolysed whey, or extensively hydrolysed casein to cow's milk formulas are needed in high-risk infants unable to be exclusively breastfed.

Partial Protein Hydrolyzed Infant Formula Decreased Food Sensitization But Not Allergic Diseases In A Prospective Birth Cohort Study

Partial Protein Hydrolyzed Infant Formula Decreased Food Sensitization But Not Allergic Diseases In A Prospective Birth Cohort Study

Growth and Tolerance of Healthy Term Infants Receiving Hydrolyzed Infant Formulas Supplemented WithLactobacillus rhamnosusGG: Randomized, Double-Blind, Controlled Trial

Healthy, term infants received extensively hydrolyzed casein formula (EHF; control), the same formula supplemented with Lactobacillus rhamnosus GG (EHF-LGG), or partially hydrolyzed whey:casein (60:40) formula supplemented with LGG (PHF-LGG), in this double-blind, randomized, controlled, parallel, prospective study. Anthropometric measures and 24-hour dietary and tolerance recalls were obtained at 30, 60, 90, 120, and 150 days of age. Blood collected in a subset of infants was analyzed for fatty acid profiles in plasma and red blood cells and for markers of allergic sensitization. Adverse events were recorded throughout the study. Growth rates were not statistically different between EHF and PHF-LGG and between EHF and EHF-LGG from day 14 to day 30, 120, or 150. No relevant differences in formula tolerance, adverse events, or allergic and immune markers were demonstrated between groups. The extensively and partially hydrolyzed formulas supplemented with LGG support normal growth in healthy, term infants and are well tolerated and safe.

Preventive effect of hydrolyzed infant formulas persists until age 6 years: Long-term results from the German Infant Nutritional Intervention Study (GINI)

Preventive effect of hydrolyzed infant formulas persists until age 6 years: Long-term results from the German Infant Nutritional Intervention Study (GINI)

Preventive effect of hydrolyzed infant formulas persists until age 6 years: Long-term results from the German Infant Nutritional Intervention Study (GINI)

The long-term effect of nutritional intervention with hydrolyzed infant formulas on allergy development has not been sufficiently evaluated. We performed a follow-up of the German Infant Nutritional Intervention study until 6 years of life to investigate the long-term allergy-preventive effect of 3 hydrolyzed infant formulas compared with cow's milk formula (CMF) in a randomized, double-blind trial. Between 1995 and 1998, 2252 newborns with atopic heredity were randomly assigned at birth to receive one of 4 blinded formulas: partially or extensively hydrolyzed whey formula, extensively hydrolyzed casein formula, or CMF as milk substitute for the first 4 months when breast-feeding was insufficient. The cohort was followed from birth until 6 years of age with yearly questionnaires. Outcomes were physician-diagnosed allergic diseases (atopic dermatitis, food allergy, allergic urticaria, asthma, and hay fever/allergic rhinitis). Log-binomial regression modeled with generalized estimation equations was used for the statistical analysis. In the intent-to-treat analysis the relative risk of a physician's diagnosis of allergic manifestation (AM) compared with CMF was 0.82 (95% CI, 0.70-0.96) for partially hydrolyzed whey formula, 0.90 (95% CI, 0.78-1.04) for extensively hydrolyzed whey formula, and 0.80 (95% CI, 0.69-0.93) for extensively hydrolyzed casein formula. The corresponding figures for atopic eczema were 0.79 (95% CI, 0.64-0.97), 0.92 (95% CI, 0.76-1.11), and 0.71 (95% CI, 0.58-0.88), respectively. In the per-protocol analysis all effects were stronger and significant. No significant effect on other AMs was found. The data confirm a long-term allergy-preventive effect of hydrolyzed infant formulas on AM and atopic eczema until 6 years of age.

Study design of the Trial to Reduce IDDM in the Genetically at Risk (TRIGR)

The hypothesis for this study is that weaning to an extensively hydrolyzed infant formula will decrease the incidence of type 1 diabetes (T1D), as it does in all relevant animal models for the disease. This will be tested in children who carry risk-associated human leukocyte antigen genotypes and have a first-degree relative with T1D. The trial will use a double-blind, prospective, placebo-controlled intervention protocol, comparing casein hydrolysate with a conventional cow's milk (CM)-based formula. A secondary aim is to determine relationships between CM antibodies, a measure of CM exposure, and diabetes-associated autoantibodies. To achieve an 80% power for the detection of a 40% intervention-induced difference in the development of autoantibodies and subsequent diabetes, the study requires 2032 subjects. A multicenter, international, collaborative effort is necessary to achieve recruitment targets. A collaborative international study group of 78 clinical centers in 15 countries has therefore been assembled for this purpose.

The Cochrane Library and dietary prevention of allergic disease and food hypersensitivity in children: an umbrella review

AbstractBackgroundDietary interventions, including avoiding allergy‐inducing foods in pregnant or lactating women and their infants, and the use dietary modifications such as prebiotics and probiotics, may prevent sensitization and subsequent allergic disease and food hypersensitivity in infants.ObjectivesTo determine the evidence from Cochrane Systematic Reviews for dietary interventions for the primary prevention of clinical allergic disease or food hypersensitivity.MethodsThe Cochrane Database of Systematic Reviews was searched for systematic reviews examining prevention of allergic disease and/or food hypersensitivity. Two reviewers independently assessed review quality, reviewed assessments of study quality and extracted reported data.Main resultsSix reviews were eligible. All reviews had concerns regarding the methodological quality of included studies and several had insufficient numbers of enrolled infants to provide precise estimates of effect. There is insufficient evidence to support the use and safety of maternal dietary allergen restriction during pregnancy and/or lactation for prevention of allergic disease in high‐risk infants. In high‐risk infants unable to be exclusively breast‐fed, there is some evidence for use of a hydrolysed infant formula for prevention of allergic disease, although the evidence is not conclusive. Evidence suggests that soy‐based infant formula should not be recommended. One trial of prebiotic supplemented formula reported a significant reduction in eczema up to 6 months of age. Meta‐analysis of 5 trials of probiotic supplements found a significant reduction in infant eczema, although trial results were heterogeneous.Authors' conclusionsIn high‐risk infants, there is no evidence to support the use of dietary interventions in pregnant or lactating women, or the use of soy‐based formula in infants for prevention of allergic disease. There is insufficient evidence to recommend the use of prebiotics or probiotics. Further trials of hydrolysed infant formula, prebiotics and probiotics are warranted. Copyright © 2007 John Wiley & Sons, Ltd.

Antiallergic Effects of Probiotics1,

A considerable part of the Western population suffers from some form of allergy, and the incidence is still rising with no sign of an end to this trend. Reduced exposure to microbial allergens as a result of our hygienic lifestyle has been suggested as one of the possible causes. It has also been suggested that probiotics may provide safe alternative microbial stimulation needed for the developing immune system in infants. This idea is supported by the fact that allergic infants have been observed to have an aberrant intestinal microbiota. They were shown to have more clostridia and fewer bifidobacteria and, in addition, to have an adult-like Bifidobacterium microbiota. Clinical trials have shown that the standard treatment of infants with atopic eczema, extensively hydrolyzed infant formula, can be significantly improved through the addition of Lactobacillus rhamnosus GG or Bifidobacterium lactis Bb-12. It has also been shown possible to halve the incidence of allergy in at-risk infants through administration of L. rhamnosus GG to expecting mothers and subsequently to their infants during the first half-year of life. Many mechanisms have been proposed for these beneficial effects, ranging from improved mucosal barrier function to direct influences on the immune system. However, the exact mode(s) of action are not yet known. For the future, elucidation of these mechanisms will be an important target. Another important area will be the investigation of interactions between probiotics and other food components that influence allergies. This will enable optimization of probiotic use for the allergic subject.

Relation between the socioeconomic status of the family and primary allergy prevention in infant feeding in Hajdú-Bihar County, Hungary

The relationship between socioeconomic status and preventive care is an important issue in public health practice in Hungary. Our aim was to investigate the association between the socioeconomic status and the present practice of primary allergy prevention in infant feeding in Hajdú-Bihar County, Hungary. A questionnaire-based cross-sectional survey was performed among 3076 infants aged 0-6 months. We studied how socioeconomic status, type of settlement, allergic background of the family and skin symptoms indicative for allergy were related to primary allergy prevention in infant feeding. Prevalence odds ratios (ORs) were calculated by multiple logistic regression. Independent determinants of breast feeding were age [OR corresponding to one month change 0.74; 95% confidence interval (CI) 0.70-0.77], the female gender (OR 1.24; 95% CI 1.06-1.46), the socioeconomic status of the family (OR comparing the worst with the best category 0.63; 95% CI 0.43-0.93), and birth weight (OR comparing <1500 g to >2500 g category 0.17; 95% CI 0.07-0.41). Among supplementary nutrient users independent determinants of the use of hydrolysed infant formulae were the socioeconomic status (OR comparing the worst with the best category 0.06; 95% CI 0.01-0.27), the type of settlement (OR comparing village with town 0.48; 95% CI 0.28-0.80), history of allergy in the family (OR 2.30; 95% CI 1.28-4.11), and skin symptoms indicative of allergy (OR 3.46; 95% CI 1.96-6.14). Socioeconomic status is related to the implementation of primary allergy prevention in infant feeding.

Clinical Study of Efficacy of a New Partially Hydrolyzed Infant Formula

Clinical Study of Efficacy of a New Partially Hydrolyzed Infant Formula

A Systematic Review of the Role of Hydrolyzed Infant Formulas in Allergy Prevention

To critically examine the published literature to determine whether feeding hydrolyzed infant formulas from birth has a role in allergy prevention. We identified data through a MEDLINE search using allergy prevention and infant formulas as indexing terms. The search was restricted to 1985 through the present, English-language articles, and human subjects. Criteria for inclusion in the review were prospective controlled trials published in peer-reviewed journals. Symptoms of allergy were defined and observed by health care providers (physicians and nurses). Nine published trials evaluated the use of extensively hydrolyzed formulas, 12 evaluated the use of partially hydrolyzed formulas in high-risk infants, and 1 evaluated the use of partially hydrolyzed formulas in an unselected infant population. The reports compared hydrolyzed formulas with breastfeeding, cow's milk formulas, soy formulas, and combinations thereof. The cohort of studies consistently showed reductions in the cumulative incidence of atopic disease from 12 to 60 months of age among high-risk infants fed extensively hydrolyzed casein formulas or partially hydrolyzed whey formulas vs cow's milk formulas. No studies showed an increase in allergy risk with any hydrolyzed formulas. Extensively hydrolyzed casein formulas and partially hydrolyzed whey formulas are appropriate alternatives to breast milk for allergy prevention in infants at risk. Because atopic disease in children cannot be predicted, the use of these formulas in the general population should be considered, and one must weigh cost, compliance, and long-term benefits.

Similar bifidogenic effects of prebiotic-supplemented partially hydrolyzed infant formula and breastfeeding on infant gut microbiota

The aim of the study was to assess the quantitative and qualitative differences of the gut microbiota in infants. We evaluated gut microbiota at the age of 6 months in 32 infants who were either exclusively breast-fed, formula-fed, nursed by a formula supplemented with prebiotics (a mixture of fructo- and galacto-oligosaccharides) or breast-fed by mothers who had been given probiotics. The Bifidobacterium, Bacteroides, Clostridium and Lactobacillus/Enterococcus microbiota were assessed by the fluorescence in situ hybridization, and Bifidobacterium species were further characterized by PCR. Total number of bifidobacteria was lower among the formula-fed group than in other groups ( P = 0.044). Total amounts of the other bacteria were comparable between the groups. The specific Bifidobacterium microbiota composition of the breast-fed infants was achieved in infants receiving prebiotic supplemented formula. This would suggest that early gut Bifidobacterium microbiota can be modified by special diets up to the age of 6 months.

PC32 DIETARY COMPLIANCE IN DIABETES PREVENTION PROJECT IN FINLAND

Introduction: Diabetes Prevention Project is an international, randomised, double-blinded trial. The hypothesis to be tested is whether hydrolysed infant formula compared to cow’s milk based formula decreases the risk of developing type 1 diabetes in children with increased genetic disease susceptibility. Eligible children have to have a family member affected by type 1 diabetes and a HLA class II genotype predisposing to type 1 diabetes. The outcome measures are emergence of type 1 diabetes associated autoantibodies and clinical type 1 diabetes. The children are followed for 10 years. Methods: During the first 6–8 months of life the infant will be given Study Formula if additional milk is needed. According to the protocol the infant should use Study Formula daily for at least 2 months before the age of 8 months, when the intervention will end at the latest. During the intervention period cow’s milk, beef and foods containing these have to be avoided. Dietary compliance is monitored with dietary interviews every month of intervention, which comprises questions on breastfeeding and use of Study Formula, allowed foods and those foods to be avoided. For the present study we used the data collected in Finland by the end of November 2003 (altogether 149 children at different stages of the intervention). Results: At 2 weeks of age 96% of the infants were breastfed and 39% were exclusively breastfed, and at the 3-month interview 83% and 29%, respectively. At the 6-month interview 60% of the children were breastfed, but only 2% were exclusively breast-fed. At 9 months of age 48% of the children were still breastfed. During the first 2 weeks of life 33% of the infants received Study Formula daily. Between 2 and 3 months of age 38% of the infants received Study Formula daily, and between 5 and 6 months of age 62%. Among the first 76 children to reach the end of the intervention 60 (79%) had received Study Formula for at least 2 months, 10 (13%) less than 2 months and 6 (8%) not at all. Of the children 22% had used food not recommended during the intervention (on average 1.2 deviations/child). The most common deviations were use of hydrolysed formula other than the Study Formula (9%), milk-based formula (8%) and milk acid bacteria that may contain trace amounts of milk protein (5%). Conclusion: These results show that a majority of the children were breastfed over the first 6 months. Exclusive breastfeeding was less common and decreased rapidly with age. The dietary compliance was good with 79% of the children receiving Study Formula for at least 2 months. A proportion of the children showed deviations from the dietary restrictions during the intervention.

Experience with a new hydrolysed feed in a paediatric gastroenterology clinic

Introduction: There are a limited number of hydrolysed feeds on the market designed to meet the specific nutritional requirements of children (Macdonald, 2001). Adult feeds are unsuitable for children as the protein content is too high and exceeds requirements (Department of Health, 1991). The energy density of hydrolysed infant formulas is inadequate for this age group: 66 kcal/100 ml vs 100 kcal/100 ml in the trial feed. Currently the only paediatric hydrolysed feed available in the UK is pork‐based and is contraindicated for some ethnic groups. This study has evaluated the use of a new feed for children based on whey hydrolysate.Method: Fifteen subjects, mean age 4.3 years (range 2.7–10.5 years), were recruited. All required a supplementary feed because they were unable to maintain good nutritional status from food alone. Ten subjects were already established on a hydrolysed or elemental feed and five had previously taken a normal diet. Eight had a diagnosis of eosinophilic enteropathy whereas others had food intolerance of unknown aetiology. Subjects were established on the new feed over 4 days and were reviewed after a 28‐day period. Weight and symptom data were recorded at the beginning and end of the trial period. One‐third of the patients were followed up for 2–5 months after completion of the trial.Results: The mean standard deviation score (SDS) for initial weight was −1.5 (range −3.92 to +0.29). After 28 days, SDS mean was −1.5 (range −4.0 to +0.17). The mean change in weight was +0.01 SDS (range −0.61 to +0.73). For children already established on hydrolysed/elemental feeds, mean SDS weight change was +0.01, whereas for patients new to an exclusion diet supplemented with trial feed the change was zero. Of eight children seven (88%) with diarrhoea improved, of three children three (100%) with vomiting improved and five of six children (83%) with abdominal pain improved during the 28‐day trial period. Nine of 15 subjects (or parents) considered that their symptoms improved and they chose to continue with the trial feed. Five of these had been receiving a hydrolysed/elemental feed and four had previously taken a normal diet. At follow‐up 2–5 months later, four of nine children remaining on the trial feed showed positive changes in weight SDS since starting the feed, one child showed a negative change and no weight data were available for the remaining four subjects.Conclusion: This new paediatric feed based on whey hydrolysate is suitable for most ethnic groups, is well accepted and tolerated and provides a more suitable nutrient profile than existing products designed for adults or infants. Objective reporting using standard symptom charts showed that symptoms had markedly improved during the trial period. The results suggest that a trial period of 1 month may not be long enough to establish the efficacy of a new feed using catch‐up growth or improvement in weight SDS as the main outcome measure.This work was supported by Nestlé Clinical Nutrition

Formulas containing hydrolysed protein for prevention of allergy and food intolerance in infants.

Allergies and food reactions are common and may be associated with foods including adapted cow's milk formulas. Formulas containing hydrolysed proteins have been used to treat infants with allergy or food intolerance, and have been advocated for prevention of allergy and food intolerance in infants. To determine whether use of hydrolysed formulas for infant feeding prevents allergy and food intolerance. If hydrolysed formulas are effective, to determine what type of hydrolysed formula is most effective including extensively and partially hydrolysed formulas. To determine which infants benefit including infants at low or high risk of allergy and infants receiving early, short term or prolonged formula feeding. The standard search strategy of the Cochrane Neonatal Review Group was used including searches of the Cochrane Controlled Trials Register (2003, Issue 1), MEDLINE (1966 - January 2003), EMBASE (1980 - January 2003) and CINAHL (1982 - January 2003) and previous reviews including cross references. Randomised and quasi-randomised trials that compare the use of a hydrolysed infant formula to human milk or cow's milk formula. Trials with >80% follow up of participants were eligible for inclusion. Eligibility of studies for inclusion, methodological quality and data extraction were assessed independently by each reviewer. Primary outcomes included clinical allergy, specific allergies and food intolerance. Meta-analysis was conducted using a fixed effects model. Eighteen trials met criteria for inclusion. No eligible trials compared prolonged hydrolysed formula to human milk feeding. Two trials compared early, short term hydrolysed formula to human milk feeding and reported no significant difference in infant allergy or childhood cow's milk allergy (CMA). Two trials compared early, short term hydrolysed formula to cow's milk formula feeding with no significant benefits reported. One large quasi-random study reported a reduction in infant CMA of borderline significance in low risk infants (RR 0.62, 95% CI 0.38, 1.00).Seven studies compared prolonged feeding of hydrolysed formula to cow's milk formula without using co-interventions for allergy prevention. Meta-analysis of 4 studies (386 infants) found a significant reduction in allergy incidence in infancy (typical RR 0.63, 95% CI 0.47, 0.85; RD -0.15, 95% CI -0.25, -0.06). One study reported a significant reduction in allergy incidence in childhood (RR 0.54, 95% CI 0.36, 0.81). Significant reductions were found in asthma prevalence in childhood, eczema incidence in infancy and prevalence in childhood, food allergy prevalence in childhood, and CMA incidence in infancy. All studies enrolled infants at high risk of allergy. Only three trials comparing prolonged hydrolysed formula feeding to cow's milk formula feeding were considered of good methodology. Only one of these trials demonstrated a benefit into childhood (5 years of age). No eligible trials examined the effects of prolonged hydrolysed formula feeding on allergy beyond early childhood. Costs were not reported. Three trials compared prolonged feeding with an extensive to a partially hydrolysed formula and reported no significant difference in allergy incidence in infancy. There is no evidence to support feeding with a hydrolysed formula for the prevention of allergy in preference to exclusive breast feeding. In high risk infants who are unable to be completely breast fed, there is evidence that prolonged feeding with a hydrolysed compared to a cow's milk formula reduces infant and childhood allergy and infant CMA. Further trials are required to determine if significant clinical benefits persist beyond 5 years of age and if there is any additional benefit from use of an extensive compared to a partially hydrolysed formula. Incremental costs of formula and the effect on compliance should be measured.

IgE-Mediated Cow's Milk Allergy: Skin Prick Test Subtypes and Clinical Phenotypes Using Cow's Milk Hydrolysate Infant Formulas

In 1986, Hill (Australia) classified group 1 children with cow's milk allergy (CMA) as having rapid onset, IgE-mediated reactions. In 1989, Schwartz (Rochester, NY) subtyped group 1 children (n = 75) into 1A, 1B, and 1C based on skin prick tests (SPTs) to non-hydrolyzed (CM—Similac®) and hydrolyzed CM infant formulas (Good Start®—partially hydrolyzed; Nutramigen®—extensively hydrolyzed). Our objective was to test the hypothesis that SPT subtypes 1A, 1B, and 1C represent different clinical phenotypes. Children with group 1 CMA (n = 170) were evaluated between 1989 and 2000. Clinical data analyzed included SPT subtype, signs, and symptoms after CM ingestion, age of onset, presence of other atopic conditions, serum CM-specific IgE, total serum IgE, and follow-up SPTs. Compared to 1A (n = 82), 1B (n = 58), and 1C (n = 30) had higher rates (p < 0.001) of systemic reactions to CM, higher (p < 0.001) serum-specific IgEs to CM proteins (α-lactalbumin, β-lactoglobulin, casein), higher prevalences of recurrent wheezing/asthma (1A = 23%, 1B = 41%, 1C = 57%; p < 0.001), and were 2.34 and 4.34 times more likely to have physician-diagnosed asthma. Prevalence of atopic dermatitis and mean total serum IgE were not significantly different. IgE-mediated CMA frequently is the first clinically identifiable allergic event in early life. SPT with CM and CM-hydrolysate infant formulas classifies these children into three SPT subtypes (1A, 1B, 1C) and two clinical phenotypes. 1A are "topical immediate reactors"—mild reactions, predominantly limited to contact urticaria and/or emesis. 1B and 1C, called "systemic reactors," are more highly sensitized and clinically reactive—generalized urticaria, angioedema, rhinitis, cough, stridor, and have an increased risk of asthma. Including CMA SPT subtypes and clinical phenotypes in future genetic studies might be informative in sorting out the relationships of the environment and child development to the phenotypic spectrum of asthma.

Dietary prevention of allergy, atopy, and allergic diseases

Dietary prevention of allergy, atopy, and allergic diseases

Routine handling of milk fed to preterm infants can significantly increase osmolality.

The purpose of these studies was to evaluate the changes in osmolality which occur in human breast milk or formula after two modifications; these changes are sometimes used in preparing these milks for consumption by premature infants, namely, the addition of fortifiers and the addition of exogenous lactase enzyme. The osmolality of expressed, previously frozen human breast milk, breast milk fortified with commercial fortifiers, liquid formulas, powdered formulas, or glucose polymers was measured. Osmolality was measured before and after warming (15 minutes at 37 degrees C) or after refrigeration at 4 degrees C for 12 hours with subsequent warming. In a second group of experiments, the osmolality of expressed breast milk and three lactose-containing formulas was measured before and after incubation with lactase (Lactaid ) at 4 degrees C for 2, 6, and 24 hours. Warming of breast milk mixed with some of the additives was associated with a significant increase in osmolality. The additives which increased osmolality included liquid glucose polymers, two commercially available powdered human milk fortifiers, and three formulas which contain glucose polymers (a protein hydrolysate infant formula powder, powdered lactose free formula, and a powdered preterm formula). Maximum increase in osmolality of breast milk occurred with the addition of 20 ml/100ml liquid glucose polymers (Polycose, Ross Laboratories) which resulted in a 21% increase in osmolality after refrigeration and warming. The addition of liquid glucose polymers and of powdered preterm formulas containing glucose polymers (Enfacare, Mead Johnson, 9.5 g/100ml and Nutramigen, Mead Johnson, 6 g/100ml) resulted in a final osmolality of over 425 mOsmol/L. The addition of lactase and subsequent incubation under refrigeration resulted in significant increases in osmolality that ranged from 25 to 66% in fortified breast milks and lactose-containing formulas. Incubation of these milks at 37 degrees for 15 minutes produced about 50% greater increase in osmolality than observed after 2 hours of incubation under refrigeration. Routine warming of breast milk with glucose polymer-containing additives, or the addition of lactase enzyme to lactose-containing feedings, can increase osmolality to levels that exceed current guidelines for premature infant feedings.