Comparison of a partially hydrolyzed infant formula with two extensively hydrolyzed formulas for allergy prevention:A prospective, randomized study

The aim of this study was to compare the allergy‐preventive effect of a partially hydrolyzed formula with two extensively hydrolyzed formulas, in infants with a high risk for development of allergic disease. High‐risk infants from four Danish centres were included in the period from June 1994 to July 1995. Five‐hundred and ninety‐five high‐risk infants were identified. High‐risk infants were defined as having bi‐parental atopy, or a single atopic first‐degree relative combined with cord blood immunoglobulin E (IgE) ≥ 0.3 kU/l. At birth all infants were randomized to one of three different blinded formulas. All mothers had unrestricted diets during pregnancy and lactation and were encouraged to breast‐feed exclusively. If breast‐feeding was insufficient, one of the three formulas, according to randomization, was given during the first 4 months. It was recommended not to introduce cow's milk, cow's milk products, and solid foods until the age of 4 months. After the age of 4 months a normal unrestricted diet and conventional cow's milk‐based formula were given when needed. All infants were followed‐up prospectively with interview and physical examination at the age of 6, 12, and 18 months, and if any possible atopic symptoms were reported. If food allergy was suspected, controlled elimination/challenge procedures were performed in a hospital setting. Of 550 infants included in the study, 514 were seen at all visits and 36 were excluded owing to non‐compliance. Of 478 infants who completed the study, 232 were exclusively breast‐fed, 79 received an extensively hydrolyzed casein formula (Nutramigen), 82 an extensively hydrolyzed whey formula (Profylac), and 85 a partially hydrolyzed whey formula (Nan HA), during the first 4 months of life. These four groups were identical in regard to atopic predisposition, cord blood IgE, birthplace, and gender. Exclusively breast‐fed children were exposed less to tobacco smoke and pets at home and belonged to higher social classes, whereas the three formula groups were identical concerning environmental factors. The frequency of breast‐feeding was high; only eight (2%) children were not breast‐fed at all. The three formula groups were identical in regard to duration of breast‐feeding and age at introduction of formula and solid foods. No significant differences were found in the three groups of infants receiving formula milk regarding the cumulative incidence of atopic dermatitis or respiratory symptoms. The cumulative incidence of parental‐reported cow's milk allergy was significantly higher in children fed partially hydrolyzed formula (Nan HA) compared with extensively hydrolyzed formula (Nutramigen or Profylac) at 12 and 18 months (NanHA, 7.1%; Nutramigen, 2.5%; Profylac, 0%; p = 0.033). The cumulative incidence of confirmed cow's milk allergy was 1.3% (three of 232) in exclusively breast‐fed infants, 0.6% (one of 161) in infants fed extensively hydrolyzed formula (Nutramigen or Profylac), and 4.7% (four of 85) in infants fed partially hydrolyzed formula (Nan HA). Partially hydrolyzed formula was found to be less effective than extensively hydrolyzed formula in preventing cow's milk allergy, 0.6% vs. 4.7% (p = 0.05), but because of the small number of cases the results should be interpreted with caution. Compared with other similar studies the frequency of atopic symptoms was low, even though the dietetic intervention did not include either maternal diet during lactation or dietary restrictions to the children after the age of 4 months.     

Prospective cohort studies using hydrolysed formulas for allergy prevention in atopy-prone newborns: a systematic review

The aim of this study is to give a systematic overview on publications having investigated the allergy preventive effect of extensively and/or partially hydrolysed infant formulas. Publications were searched by several strategies. Inclusion criteria were: prospective cohort study, randomisation, family history of atopy of the subjects, follow-up for at least the 1st year of life. Studies were described systematically as to methods, study participants, interventions and co-interventions, and study outcomes. The methodological quality was judged according to an instrument assessing the reduction of bias (score between 0 and 7 points). Data of studies having examined partial hydrolysates are presented as odds ratios. Of 16 studies found, 10 fulfilled the inclusion criteria. Study designs showed considerable differences as to methods, intervention and co-intervention procedures and definition of outcomes. Methodological quality varied between 0 and 6 points. The comparison of exclusively test- and control formula-fed groups showed a uniform tendency towards allergy protection in studies with partial hydrolysates. Study results on the effect of extensive hydrolysates were not comparable because of major differences in study designs. Conclusion More well-designed studies with an adequate statistical power are needed to compare the allergy preventive effect of partially and extensively hydrolysed formulas with a standard infant formula. Received: 17 May 2000 / Accepted: 30 January 2001     

水解蛋白婴儿配方研究进展

牛奶过敏足婴幼儿最主要的食物过敏类型,1岁以内婴幼儿大约有2.5%的人群表现牛奶过敏.以天然牛奶蛋白为基础的水解蛋白配方,其变应原性降低,其中部分水解蛋白配方(pHF)可诱导口服免疫耐受,主要用于预防婴儿食物过敏和特应性皮炎;深度水解配方主要用于治疗婴儿牛奶过敏;严重牛奶过敏导致生长发育障碍的患儿,应用氨基酸配方治疗.     

Use of infant formulas in infants with cow milk allergy

Allergic (immune-mediated) reactions to cow milk and other dietary proteins encountered during infancy are responsible for some of the adverse symptoms and syndromes observed in infants intolerant to cow milk, infant formulas and occasionally human milk. Iron deficiency anemia associated with gastrointestinal blood loss, protein losing enteropathy, enterocolitis, colitis, and malabsorption syndrome are examples of putative allergic reactions to dietary antigens which occur in infancy. A number of symptoms referable to the gastrointestinal tract such as, vomiting, colic and chronic non-specific diarrhea occur in infants both with and without immune-mediated reactions to dietary antigens. Verification of adverse reactions to dietary antigens, including allergic reactions, should be accomplished through the use of double-blind, placebo-controlled food challenge, with the dietary antigen to be tested presented in a liquid vehicle or, in older children, in capsule form. Approximately 8%–25% of children with immediate hypersensitivity to cow milk have been found to be allergic to soy products. Soy and other intact protein substitutes for cow milk, such as beef and lamb based formulas, have produced anaphylactic reactions both in human infants and in animal models. Hypoallergenic formulas should have a chemically modified protein base which demonstrates significant reduction in anti-genicity when tested in the laboratory both in vitro and in vivo. Such formulas should meet rigorous standards for hypoallergenicity in clinical testing in human allergic infants or infants at high risk for developing allergy before being labelled hypoallergenic.     

Extensively and partially hydrolysed infant formulas for allergy prophylaxis

The allergy preventive effect of extensively (N) and partially (PH) hydrolysed cows' milk formulas compared with a regular formula (RM) was assessed in 155 infants with a family history of allergy. No cows' milk was given during the first nine months of life and no egg and fish up to 12 months of age. Breast feeding mothers avoided the same foods. At weaning the infants were randomised to one of the formula groups. The cumulative incidence of atopic symptoms at 18 months was 51, 64, and 84% in the N, PH, and RM groups, respectively. From 6 to 18 months there were significantly less cumulative atopic symptoms in the N group compared with the RM group, and significantly less than the PH group up to 6 (N = 25%; PH = 46%) and 9 months (N = 34%, PH = 58%). At 9 months significantly fewer infants in the N group (10%) than in the PH group (33%) had a positive skin prick test to eggs. The findings support an allergy preventive effect of an extensively hydrolysed formula, but not of a partially hydrolysed formula, during the first 18 months of life of high risk infants.     

Extensively and partially hydrolysed infant formulas for allergy prophylaxis

Accepted 17 March 1997The allergy preventive effect of extensively (N) and partially (PH) hydrolysed cows'' milk formulas compared with a regular formula (RM) was assessed in 155 infants with a family history of allergy. No cows'' milk was given during the first nine months of life and no egg and fish up to 12 months of age. Breast feeding mothers avoided the same foods. At weaning the infants were randomised to one of the formula groups. The cumulative incidence of atopic symptoms at 18 months was 51, 64, and 84% in the N, PH, and RM groups, respectively. From 6 to 18 months there were significantly less cumulative atopic symptoms in the N group compared with the RM group, and significantly less than the PH group up to 6 (N= 25%; PH = 46%) and 9 months (N = 34%, PH = 58%). At 9 months significantly fewer infants in the N group (10%) than in the PH group (33%) had a positive skin prick test to eggs. The findings support an allergy preventive effect of an extensively hydrolysed formula, but not of a partially hydrolysed formula, during the first 18 months of life of high risk infants.     

Protein hydrolysates: hypoallergenic milks and extensively hydrolyzed formulas. Immuno-allergic basis for their use in prevention and treatment of milk allergy]

Allergy to milk has an estimated incidence of 2.5%. Hypoallergenic milks are partial hydrolysates of proteins with lactose. Extensive hydrolysates of casein are mainly small peptides and do not include lactose in their formula. A primary allergenicity as well as a cross-sensitivity are shown for all partial hydrolysates. Even extensive hydrolysates have a weak potential of cross-allergy. The prevention of cow's milk allergy in infants at peculiar risk, born from atopic parents, is based on breast-feeding and/or partial or extensive hydrolysates. There is no conclusive evidence for the usefulness of eviction of dairy products during pregnancy or during the period of breast-feeding. The treatment needs exclusively extensive casein hydrolysates ensuring a 90% protection with 95% confidence intervals. Predictive prick tests in certain cases may help the choice of another hydrolysate. Severe cases with failure to thrive or multiple food intolerance require an amino-acid based formula (Neocate). A rational diversification of the diet is advised in order to prevent the onset of a multiple food intolerance syndrome which could avert from the recovery of cow milk allergy.     

Galacto-oligosaccharides and long-chain fructo-oligosaccharides as prebiotics in infant formulas: A review

The present review summarizes clinical and experimental data concerning the possible effects of a prebiotic mixture of short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides. The results from several studies, made up of over 400 preterm and term infants, clearly demonstrate that the prebiotic mixture under examination specifically stimulates the growth of bifidobacteria and lactobacilli and reduces the growth of pathogens. As a consequence of the changed intestinal flora by the dietary galacto-oligosaccharides and fructo-oligosaccharides, the faecal pH values and the short-chain fatty acid pattern were similar to those found in breastfed infants. In addition, the stool consistency was the same as in breastfed infants. In vitro experiments have demonstrated that the specific short-chain fatty acid pattern, at a pH similar to that found in faecal samples of breastfed infants, reduces the growth of pathogens in a dose-dependent manner but does not influence the growth of bifidobacteria and lactobacilli. In an animal vaccination model, the prebiotic mixture improved the response to vaccination. In an allergy model (sensitization by ovalbumin), the allergic reaction was reduced by the prebiotic mixture. The data obtained from animal experiments are in agreement with preliminary data from clinical trials which indicate a reduced allergic response (reduced plasma IgE/IgG4 ratio) and reduced episodes of upper airway infection during the first year of life.
Conclusion: Experimental evidence demonstrates that the prebiotic mixture employed in these studies modulates the intestinal flora and modulates the immune system as human milk does. There are sufficient experimental data to put forward the hypothesis that substances like the prebiotic mixture under study will substantially contribute to the improvement of the protective properties of infant formulas.     

Efficacy and safety of hydrolyzed rice-protein formulas for the treatment of cow's milk protein allergy

Foods for special medical purposes (FSMPs) with a protein fraction made of hydrolyzed rice protein (HRPs) have been on the market in Europe since the 2000s for the treatment of cow's milk protein allergy (CMPA). HRP formulas (HRPFs) are proposed as a plant-based alternative to cow's milk protein-based extensively hydrolyzed formulas (CMP-eHF) beside the soy protein formulas whose use in CMPA is controversial. HRPFs do not contain phytoestrogens and are derived from non-genetically modified rice. HRPFs are strictly plant-based apart from the addition of vitamin D₃ (cholecalciferol). As the amino acid content of rice proteins differs from that of human milk proteins, the protein quality of these formulas is improved by supplementation with free lysine, threonine, and tryptophan. The consumption of HRPFs has risen: for example, in France HRPFs account for 4.9% in volume of all formulas for children aged 0–3 years. Several studies have shown the adequacy of HRPFs in treating CMPA. They ensure satisfactory growth from the 1st weeks of life for infants and toddlers, both in healthy children and in those with CMPA. HRPFs can be used to treat children with CMPA either straightaway or in second intention in cases of poor tolerance to CMP-eHF for organoleptic reasons or for lack of efficacy. In France, the cost of HRPFs is close to that of regular infant or follow-on formulas.     

水解蛋白配方与婴幼儿牛奶过敏的预防和治疗

食物过敏是婴幼儿最早出现的过敏问题,牛奶是婴幼儿最常见的过敏食物。牛奶过敏的临床表现多种多样,可涉及皮肤、呼吸道、消化道等多器官多系统。母乳喂养是过敏高风险婴儿的首选喂养方式,但对不能进行母乳喂养的婴儿应选择适当的低敏配方奶,水解蛋白是获得低敏配方的最好方法。根据水解的程度,水解蛋白配方分为适度水解蛋白配方和完全水解蛋白配方。完全水解配方被推荐用于牛乳蛋白过敏婴儿的治疗,适度水解配方通常推荐用于特应质高风险婴儿的初级干预。     

婴幼儿食物过敏的影响因素和防治现状

食物过敏是婴幼儿最早和最常见的过敏性疾病,近年来发病率呈上升趋势,不仅影响患儿生长发育,同时与其他过敏性疾病的发生密切相关.因此,了解婴幼儿食物过敏的发生机制和相关影响因素,研究疾病的预防和治疗,并探讨其预后对其他相关过敏性疾病的影响对于变态反应性疾病的研究有重要作用.     

Osmolalities of infant formulas

The osmolalities of breast milk and of 36 products that may be fed to infants were determined by the freezing-point depression method. A wide range of osmolality was observed among formulas that provide 67 kcal/100 ml, and many have osmolalities greater than 400 mOsm/kg of water. Reconstituted powdered formulas have osmolalities that are widely varied from batch to batch, are greater when prepared by scoop measures when the osmolalities of corresponding ready-to-feed formulas, and are greater than the osmolalities of the formulas prepared by weighed measures from the manufacturer's formulation. The osmolality of products for oral consumption should be considered in the selection of formulas for preterm infants.     

A systematic review of lay views about infant size and growth

Objectives

To understand lay views on infant size and growth and their implications for a British population.

Methods

A systematic review of parental and other lay views about the meanings and importance of infant size and growth using Medline, PsycInfo, CINAHL, Sociological Abstracts, IBSS, ASSIA, British Nursing Index ChildData, Caredata, SIGLE, Dissertation Abstracts (US), Index to Theses. 19 studies, most of which reported the views of mothers, from the US, Canada, the UK and Finland were reviewed.

Results

Notions of healthy size and growth were dominated by the concept of normality. Participants created norms by assessing and comparing size and growth against several reference points. When size or growth differed from these norms, explanations were sought for factors that would account for this difference. When no plausible explanation could be found, growth or size became a worry for parents.

Conclusions

Parents consider the importance of contextual factors when judging what is appropriate or healthy growth. For public health advice to be effective, lay, as well as scientific, findings and values need to be considered.Growth and size in infancy matter to parents and professionals. Intervention in infancy has the potential to promote health throughout the life course.¹ Although the benefits (or otherwise) of early interventions may not be realised for many years, the beliefs and behaviours of individual lay persons (in this case, particularly parents) will affect the uptake of policy or interventions immediately. As Harden et al² point out, bringing together views and studies in a systematic way may deepen our understanding of public health issues. Systematic reviews also represent good stewardship in terms of the time of both participants and researchers.This paper describes a systematic review designed to understand lay (particularly parental) views of infant size and growth.