Hydrolyzed Formula Research Articles

Hydrolysed milk in preterm infants: An open problem

To review knowledge about the role, indications and nutritional adequacy of protein hydrolysate formulas (HF) in the preterm newborn. A review of the available literature was carried out. No data support the use of HF for atopy prevention. HF could have a positive role in the early feeding of very-low-birthweight infants, but several concerns exist about their nutritional adequacy. Further investigations addressing protein and mineral metabolism as well as long-term effects, including neurodevelopment, are needed.

FECAL CALPROTECTIN AND COW'S MILK PROTEIN ALLERGY IN INFANTS

Calprotectin, a 36.5 kiloDalton protein released into the intestinal lumen by macrophages and neutrophils, has been shown to be useful in determining disease activity and treatment response in intestinal inflammatory conditions such as inflammatory bowel disease. Cow's milk protein allergy (CMPA) is a common gastrointestinal problem of infancy associated with rectal bleeding, emesis, diarrhea, and eczema. We hypothesized that fecal calprotectin is a useful screening test to evaluate for resolution of CMPA in infants. A pilot trial was performed in six infants less than 90 days of age with rectal bleeding and other symptoms consistent with cow's milk protein allergy. Fecal calprotectin levels were determined by ELISA assay at baseline, 3, and 6 weeks after placement on a protein hydrolysate formula. All infants improved clinically and rectal bleeding resolved within 6 weeks after conversion to a hydrolysate formula. Initial fecal calprotectin levels ranged from 135-1537 mg/L (mean 557 mg/L) and decreased to a range of 42-219 mg/L (mean 163 mg/L) after 6 weeks on protein hydrolysate formula. A control patient with no symptoms of CMPA maintained fecal calprotectin values between 97 and 129 mg/L throughout the study. The results of this pilot trial suggests that fecal calprotectin may be a useful screening test for treatment response to protein hydrolysate formula; however, further studies with a larger number of patients are necessary to determine the utility of this test in infants with CMPA.

Gastrointestinal Manifestations of Food Allergies in Pediatric Patients

Foods that account for 90% of allergic reactions in children are cow's milk protein, eggs, peanut, soy, tree nuts, fish, and wheat. Food allergy can manifest as urticaria/angioedema, anaphylaxis, atopic dermatitis, respiratory symptoms, or a gastrointestinal (GI) disorder. GI allergic manifestations can be classified as immunoglobulin E (IgE) mediated (immediate GI hypersensitivity and oral allergy syndrome); "mixed" GI allergy syndromes (involving some IgE components and some non-IgE or T-cell-mediated components) include eosinophilic esophagitis and eosinophilic gastroenteritis. Non-IgE-mediated or T-cell-mediated allergic GI disorders include dietary protein enteropathy, protein-induced enterocolitis, and proctitis. All these conditions share a common denominator: the response of the immune system to a specific protein leading to pathologic inflammatory changes in the GI tract. This immunological response can elicit symptoms such as diarrhea, vomiting, dysphagia, constipation, or GI blood loss, symptoms consistent with a GI disorder. The detection of food allergies can be accomplished by the use of radioallergosorbent (RAST) testing and skin prick tests in helping to assess the IgE-mediated disorders. Patch tests may help evaluate delayed hypersensitivity reactions. Treatment of GI allergic disorders ranges from strict dietary elimination of offending food(s), use of protein hydrolysates, and use of L-amino acid-based formula when protein hydrolysates fail. Treatment with topical (for eosinophilic esophagitis) or systemic steroids is used if all dietary measures are unsuccessful. Maternal breast feeding or the use from birth of hydrolysate formulas (extensive or partial hydrolysates) may be efficacious in the prevention of atopic disease in "high-risk" families (with at least 1 parent or sibling with a history of atopic disease).

Z‐score of weight for age of infants with atopic dermatitis and cow's milk allergy fed with a rice‐hydrolysate formula during the first two years of life

Recently, rice-based formulas have been widely used in hypoallergenic diets, but data on nutritional values are scarce. To evaluate the growth of infants fed with a rice-based hydrolysate formula, compared to those infants fed with a soy formula or an extensively hydrolysed casein formula, in the first 2 y of life. A total of 88 infants were enrolled between March 2002 and March 2004. Fifty-eight infants with atopic dermatitis (AD) and cow's milk allergy (CMA), confirmed by open challenge, were enrolled as study group: 15 were fed with a rice-based hydrolysate formula (RHF), 17 with a soy-based formula (SF) and 26 with an extensively hydrolysed casein formula (eHCF). Thirty infants with AD without cow's milk allergy were recruited as a control group (CG) and fed with a free diet. Weight was recorded on enrolment and at 3-monthly intervals in the first year of life, and at 6-monthly intervals in the second year. Infants were weighed naked, before feeding, by means of an electronic integrating scale. The z-scores of weight for age were calculated. One-way analysis of variance and Student's t-test were used for statistical comparison. Significance was set at p<0.05. No significant differences between the RHF, SF and eHCF groups were observed for the z-score of weight for age during the first 2 y of life, but a significantly lower difference was seen in the RHF group compared to the control group in the intervals 9 mo-1 y (p=0.025) and 1-1.5 y (p=0.020) of age. In contrast, the SF and eHCF groups were comparable to the control group, but the eHCF group was significantly lower (p=0) in the first trimester of life. Even if our findings show no significant difference between RHF and control, low weight observed in infants fed with RHF raises doubts about the nutritional adequacy of rice-hydrolysate formulas.

Which milk for the sick preterm infant?

Summary Understanding the nutritional needs of the sick preterm infant will ensure that nutritionally adequate milks are used, but to minimise complications an understanding of the interaction between milk composition and neonatal gastrointestinal physiology is required. Unmodified preterm breast milk is probably the safest milk, but might require supplementation with fortifiers to meet nutritional needs. Fortification affects the osmolarity, protein and mineral content of breast milk in ways that can have adverse effects on intestinal function. Although preterm formulas meet the nutritional requirements of sick preterm infants, formula milk is associated with an increased risk of necrotising enterocolitis. Hydrolysate and elemental formulas have a role in treating established malabsorption, dysmotility or obstruction, but they are nutritionally inadequate for the sick preterm baby and have features which make them unsuitable for the prevention of gastrointestinal disease. In some circumstances, the use of minimal or partial enteral nutrition can help to maintain nutrition in the particularly sick infant, in which case the nutritional content of the milk will be less critical.

Primary prevention of food allergy in infants who are at risk

Allergic diseases represent a major burden of health problems in industrialized countries. Though several studies have focused on possible preventive measure and strategies much controversy still exists on this topic. The aim of this review is to discuss the recent literature on primary prevention of food allergy. In prospective observational controlled studies of high quality of birth cohorts, exclusive breastfeeding for at least 4 months combined with introduction of solid foods after 4 months of age is associated with a reduced risk of food allergy and atopic dermatitis, particularly in high-risk infants. When breastfeeding for 4-6 months is not possible or insufficient, randomized controlled trials have shown a significant reduction in food allergy and atopic dermatitis in high-risk infants fed a documented hypoallergenic hydrolysed formula. Breastfeeding should be encouraged for 4-6 months. In high-risk infants a documented hypoallergenic hydrolysed formula is recommended if exclusively breastfeeding is not possible for the first 4 months. As regards primary prevention of food allergy there is no evidence for preventive dietary intervention during neither pregnancy nor lactation. Likewise, preventive dietary restrictions after the age of 4-6 months are not scientifically documented.

Neonatal Nutritional Interventions in the Prevention of Type 1 Diabetes

After completing this article, readers should be able to: 1. Outline the current concepts of the pathogenesis of type 1 diabetes (T1D) with regard to dietary triggers and genetic susceptibility. 2. Discuss the evidence, both epidemiologic and that derived from studies of animal models, that supports the association between infant feeding practices and T1D. 3. Describe the roles for intestinal immunity and permeability in supporting the hypothetical model of cow milk protein mediation of T1D autoimmunity. 4. Delineate the goals and rationale for prospective clinical trials evaluating neonatal nutrition and the development of T1D. 5. List the putative dietary modulators of T1D. Type 1 diabetes (T1D), a disease that has unacceptably high morbidity and mortality, is increasing in incidence, prompting the redoubling of efforts toward its prevention. Progress toward prevention and cure relies on elucidation of the disease’s pathogenesis, which, to date, has remained poorly defined. The defining features of T1D, insulin deficiency and hyperglycemia, result from an immune-mediated destruction of insulin-secreting beta cells in the pancreatic islets. The loss of beta cell mass is believed to be gradual for most individuals, accounting for the sometimes prolonged asymptomatic periods of autoimmunity preceding overt diabetes (Fig. 1). Indeed, the chronic autoimmune nature of the disease is well established, as is the genetic predisposition. Specific associations with molecules of the human lymphocyte antigen (HLA) define both susceptibility to and protection from T1D. However, T1D is a polygenic disorder with more than 20 loci associated with susceptibility or resistance to the disease, of which the HLA may account for less than 50% of the genetic predisposition. Genetics clearly comprises a major component of the development of T1D, but the interaction between the environment and the immune system abnormalities is believed to weigh heavily in disease development. Indeed, trends in T1D incidence, both geographic and temporal, suggest a strong …

MANAGEMENT OF ACUTE GASTROENTERITIS IN FRANCE BY PAEDIATRICIANS AND GENERAL PRACTITIONERS:WHAT??S RECOMMENDED AND WHAT??S PRACTICED

Aim: The ESPGHAN Working Group on acute diarrhoea and the French Speaking Group (GFHGNP) published recommendations with specific emphasis on oral rehydration, early refeeding and avoidance of ineffective drugs. We conducted a study to determine how closely physicians in France follow the treatment guidelines. Methods: Observational prospective study: 1 November 2003-29 February 2004. Children were included if they presented at least 3 watery stools per day. Physicians were fully free for their prescriptions Results: 1602 children (<4 months: n = 88) (5 months to 3 years: n = 605) (3-15 years: n = 909) were treated by 332 general practitioners (GP) and 206 paediatricians (P). For children <18 months of age, dehydration was graded: <5% in 78.7%, 5 to 10% in 20.6% and >10% in 0.6%. Oral Rehydration Solutions were prescribed in solely 70% of the cases. 62% of responding physicians extend the rehydration period to 12 to 24 hours. Refeeding was initiated within 4 h in 54.7%, within 4-8 h in 21.8%, within 8-12 h in 12.6%, within 12-24 h in 8% and after 24 h in 2.7%. The current milk was stopped in 66.4% of children. In these cases, formula was changed for a lactose-free formula (63.8%), a low containing lactose formula (14.9%), a protein hydrolysate (13.3%) and various formulas including probiotics (8%). Regarding all children (1month-15 years; n = 1602), one drug at least was prescribed in 96% of cases with a mean of 2.4 drugs per child: domperidone (86.4%), racecadotril (35.1%), lactobacillus acidophilus (27.1%), smectite (25.2%),nifuroxazide (6.8%) and antibiotics (0.7%) Summary: Globally, P and GP in France all act alike in the management of acute diarrhoea in children with two exceptions: significantly more GP stop milk feeding until 12-24 h and change formula when significantly more P advance to a full strength concentration with the same formula within 8 h. Conclusions: One more time, this study demonstrates that we are still far from the ESPGHAN guidelines for optimal management of acute gastroenteritis, particularly regarding ORS and drugs prescription.

A SURVEY OF ENTERAL FEEDING PRACTICES IN PATIENTS WITH SHORT BOWEL SYNDROME IN THE UNITED KINGDOM

Aim: There is no consensus amongst clincians who manage patients with Short Bowel Syndrome (SBS) on the most appropriate enteral feeds and introduction of solids. Method: A questionnaire was sent to all dietitians (40) who are Associate Members of the British Society of Paediatric Gastroenterology, Hepatology and Nutrition to ascertain their current practice on the type of enteral feeds used, monitoring tolerance of feeds, anthropometry, the use of novel substrates (pectin, glutamine, pre and probiotics), and the introduction of solids in the management of patients with SBS. Results: Breast milk was the most commonly used feed initially. 68% of dietitians then used a hydrolysed protein formula when tolerance became a problem. Continuous feeds were given initially in 66% of patients. The most common reason for changing the type of feed was increased stool frequency, the presence of fat or reducing substances in stools and poor weight gain. 62% of dietitians occasionally used a modular feed. Weight was most commonly measured twice weekly, length/height and head circumference monthly. 80% of dietitians did not measure Mid-arm Circumference or Triceps skinfold thickness. 4 centres followed set protocols for biochemical monitoring. Investigations in other centers varied. Novel substrates were infrequently used. Solids were most commonly introduced at 6 months for patients on parenteral nutrition and between 5-6 months for those who were on complete enteral feeds. Exclusion of milk, gluten, eggs and soya varied between centres. Conclusion: Practice throughout the United Kingdom varied immensely on the dietetic management of patients with SBS with each unit following their own protocols and personal practice. A more consistent approach to the nutritional management of SBS patients should be pursued.

Dietary manipulation of beta cell autoimmunity in infants at increased risk of type 1 diabetes: a pilot study

We aimed to assess the feasibility of a dietary intervention trial with weaning to hydrolysed formula in infants at increased risk of type 1 diabetes and to study the effect of the intervention on the emergence of diabetes-associated autoantibodies in early childhood. We studied 242 newborn infants who had a first-degree relative with type 1 diabetes and carried risk-associated HLA-DQB1 alleles. After exclusive breastfeeding, the infants underwent a double-blind, randomised pilot trial of either casein hydrolysate (Nutramigen; Mead Johnson) or conventional cow's milk-based formula until the age of 6-8 months. During a mean observation period of 4.7 years, autoantibodies to insulin, anti-glutamic acid decarboxylase and insulinoma-associated antigen-2 were measured by radiobinding assays, and islet cell antibodies (ICA) by immunofluorescence. The feasibility of screening and identifying a cohort of first-degree relatives with HLA-conferred disease susceptibility, enrolling them in a dietary intervention trial and following them for seroconversion to autoantibody positivity is established. The cumulative incidence of autoantibodies was somewhat smaller in the casein hydrolysate vs control formula group, suggesting the need for a larger well-powered study. After adjustment for duration of study formula feeding, life-table analysis showed a significant protection by the intervention from positivity for ICA (p=0.02) and at least one autoantibody (p=0.03). The present study provides the first evidence ever in man, despite its limited power, that it may be possible to manipulate spontaneous beta cell autoimmunity by dietary intervention in infancy.

Understanding the Origin of Flavor Preferences

Food traditions mirror a people’s beliefs and values and are among the last characteristic of a culture that is lost during the immigration of an individual or group into a new culture (Rozin, 1996). However, the origins of preferences and aversions for flavors and food in humans have elicited much speculation but, until recently, remarkably little experimental investigation (Ganchrow and Mennella, 2003). We now know that initial experiences with flavors occur prior to birth when the flavor of amniotic fluid changes as a function of the mothers’ dietary choices (Mennella et al., 1995). Some of these same flavors continue to be experienced in mother’s milk (Mennella and Beauchamp, 1991). Because early flavor experiences have been shown to enhance acceptance and enjoyment of foods during weaning and childhood (Mennella et al., 2001), culturally determined flavor preferences, one of the most enduring characteristic of an ethnic group, can be understood in the context of early flavor exposure. The major factor that has inhibited even greater progress in understanding the origin of flavor preference is the absence of a robust paradigm to investigate the role of infant experience. Practically, it is difficult experimentally to vary the flavor experiences of infants and children over long time periods and so few studies investigating consequences of major differences in feeding experience have been conducted (Mennella et al., 2001). What is needed is a naturally occurring flavor variation that can be exploited to investigate the effects on subsequent acceptance. During the past decade, we have identified a convenient and powerful model system to study the origin of flavor preferences—infants’ acceptance of formulas containing protein hydrolysates, the feeding regimen of choice for formula-fed infants who cannot tolerate cows’ milk and other intact proteins (American Academy of Pediatrics, Committee on Nutrition, 1989). It is perhaps one of the most striking examples of a developmental change in chemical sensory perception. Although this type of formulas is extremely unpalatable to older children and adults because of its offensive flavor, infants 4 months of age or younger accept it without difficulty (Mennella and Beauchamp, 1991, 1996). However, if infants receive exposure by the third month of life, they continue to accept these formulas for a considerable period of time thereafter (Mennella et al., 2003). From these data, we hypothesized that there is an early sensitive period during which the hedonic value of this formula—and likely the flavors of other foods and beverages—is established. The overall goal of the present study was to explore the specificity of the flavor experience during this sensitive period. Although all brands of protein hydrolysate formula share common flavor attributes and are judged unpleasant by adults, they differ in their flavor profiles. Here we exploit the inherent flavor variation of different brands of formulas to determine whether experience with one brand of protein hydrolysate formula influences acceptance of another brand that differs in flavor. In other words, is the acceptance pattern that develops specific to the flavor profile experienced? Or does the infant, regardless of the brand of formula currently being fed, prefer the one that tastes sweeter or the one that tastes less bitter? To this aim, we studied infants’ acceptance of two commercial brands of hydrolysate formulas widely used in the Philadelphia area of the United States: Alimentum™and Nutramigen™.

Allergie aux protéines du lait de vache après chirurgie digestive néonatale

Cases of cow’s milk protein allergy have been occasionally reported after neonatal intestinal surgery. Aim of the study. – To measure the prevalence of cow’s milk protein allergy (CMPA) following neonatal intestinal surgery. Patients and methods. – The files of all children who underwent intestinal surgery in the neonatal period over a four-year-period were reviewed. The diagnosis of CMPA was made on the association of one or several symptoms suggesting food allergy after the introduction of cow’s milk protein in the diet, the disappearance of the symptoms after exclusion of cow’s milk protein from the diet and their reappearance after reintroduction of cow’s milk protein. Results. – During the study period, 251 neonates underwent an intestinal surgery. Among them, 11 babies (4.3%) developed CMPA. None of them had a medical history of family atopy. Moreover, while 5 children were fed with a diet containing cow’s milk protein before surgery : none of them presented initially with symptoms suggesting CMPA before intestinal surgery. Small intestine suffering was observed during operation in seven of 11 patients. No specific neonatal digestive disease or malformation was associated with CMPA. The signs revealing CMPA were primarily digestive : diarrhoea ( N =3), vomiting ( N =4), abdominal distension ( N =2), colic or anorexia ( N =2). Casein specific immunoglobulin E were present in nine of ten cases, α lactalbumin and/or β lactoglobulin specific immunoglobulin E were present in six of ten cases. Prick test were performed in three children and were positive. Conclusion. – The high prevalence of CMPA among these patients with no risk factors of allergy raises the question of the role of neonatal intestinal surgery in developing food allergy. These data should be confirmed by prospective case-control studies. They underline the interest to evoke the diagnosis of CMPA when digestive symptoms occur after milk protein introduction in children undergoing neonatal intestinal surgery. Breast feeding or milk protein hydrolysate formula should be used for refeeding these patients.

Soy formula for prevention of allergy and food intolerance in infants.

Allergies and food reactions in infants and children are common and may be associated with foods including adapted cow's milk formulas. Soy based formulas have been used to treat infants with allergy or food intolerance. However, it is unclear whether they can be advocated for the prevention of allergy and food intolerance in infants without clinical evidence of allergy or food intolerance. In infants without clinical evidence of allergy or food intolerance, to determine whether feeding them an adapted soy formula compared to human milk, cow's milk formula or a hydrolysed protein formula prevents allergy or food intolerance. The standard search strategy of the Cochrane Neonatal Review Group was used including searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2003), MEDLINE (1966 - January 2004), EMBASE (1980 - January 2004), CINAHL (1982 - December 2003) and previous reviews including cross references. Randomised and quasi-randomised trials that compare the use of an adapted soy formula to human milk, an adapted cow's milk or a hydrolysed protein formula for infant feeding in the first 6 months. Only trials with > 80% follow up of participants and reported in group of assignment 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 where no heterogeneity of treatment effect existed, and a random effects model when heterogeneity was found. Five eligible studies were found, all enrolling infants at high risk of allergy on the basis of a family history of allergy in a first degree relative. All studies compared use of a soy to a cow's milk formula. Two studies also included a group fed a formula containing hydrolysed protein. No eligible study enrolled infants fed human milk. No study examined the effect of early, short term soy formula feeding. Three studies were of good methodology and did not have unbalanced allergy-preventing co-interventions in the treatment groups. Comparing soy to cow's milk formula, one study with unclear allocation concealment and 19.5% losses to follow up reported a reduction in cumulative incidence of childhood allergy, asthma and allergic rhinitis. No other study reported a significant benefit for any allergy or food intolerance. Analysis found no significant difference in allergy cumulative incidence in infancy (one study: RR 1.02, 95% CI 0.69, 1.49) or childhood (3 studies: typical RR 0.73, 95% CI 0.37, 1.44) and no significant difference in cumulative incidence or period prevalence of any specific allergy or food intolerance in infancy or childhood. Analysis of studies comparing soy to a hydrolysed formula found a significant increase in infant (one study: RR 1.67, 95% CI 1.03, 2.69) and childhood allergy cumulative incidence (one study: RR 1.55, 95% CI 1.02, 2.35), infant eczema cumulative incidence (2 studies: typical RR 2.34, 95% CI 1.51, 3.62) and childhood food allergy period prevalence (one study: RR 1.81, 95% CI 1.09, 3.02). Feeding with a soy formula should not be recommended for the prevention of allergy or food intolerance in infants at high risk of allergy or food intolerance.

P1125 A RANDOMISED TRIAL TO EVALUATE THE NUTRITIONAL EFFICACY OF A HYPOALLERGENIC INFANT FORMULA CONTAINING A NEW PROTEIN HYDROLYSATE

Introduction: Hypoallergenic (HA) infant formula is widely used to prevent allergy in at risk children. Aptamil HA1 (Milupa GmbH) is currently used for this purpose. A new protein hydrolysate for Aptamil HA1 was developed by the company which was prepared from 100% low threonine whey in place of 50% casein and 50% conventional whey. The two protein hydrolysates otherwise had similar amino acid pattern and molecular weight profiles. Since the change in manufacturing process might influence the nutritional quality, we conducted a study to compare the effect of the new versus the classical formula on growth, acceptability and tolerability. Methods: Healthy newborn term infants were randomised to receive blind either Aptamil HA1 with the standard hydrolysate (formula S) or new hydrolysate (formula N). Median birth weight (range) was respectively 3180g (2150–3960) and 3260g (2470–4420). The primary endpoint was weight gain at weeks 6 and 13. Secondary endpoints included length gain, head circumference gain and mothers’ perceptions of formula performance. Results: Fifty-three children were randomised. The two groups were well balanced for all studied baseline parameters. At week 13 the median weight gain was significantly higher in group N (table). There were no differences in the gains in length or head circumference. We found no differences regarding the intakes of additional food and drink, the characteristics of stools or adverse events. Mothers’ impressions did not differ except concerns about possetting were slightly higher in group N (p<0.05), although regurgitations were observed less frequently in that group by the paediatrician.Table 1: Median gain [range]Conclusion: This study demonstrates that the new formula supports a satisfactory growth pattern and a slightly higher weight gain compared to previous Aptamyl HA1 formula. The weight gains observed are similar to previously published values for formula-fed infants. The acceptability characteristics of the two formulas were similar.

P0945 HELICOBACTER PYLORI INFECTION IN THE NEONATAL PERIOD AND COW MILK PROTEIN INTOLERANCE: IS THERE A RELATION?

Introduction: H. pylori is one of the most common infections worldwide, and especially in developing countries. It is generally accepted that H. pylori is most often acquired in childhood. However, under one year of age, infants rarely become infected with H. pylori, even when they are exposed to infected mothers. Many groups have reported a maternal transfer of H. pylori-specific IgG antibodies to the fetus. Spontaneous clearance followed by subsequent reacquisition of infection in young children also has been reported. Methods: The aim of this study is the retrospective analysis of 3 cases of H. pylori infection in neonates between 2001 and 2003, and to discuss the associated clinical presentation along with the need of eradication therapy in this age group. Results: The patients had 15, 17 and 18 days respectively. The first patient presented with excessive crying. The two others had symptoms of gastric outlet syndrome, with poor weight gain and malaise. Treatment for GERD (prokinetics and anti-acids) was initiated in patients 1 and 3, and patient 2 received only prokinetic therapy with hydrolysate formula, then amino-acid formula, with no clinical improvement in all patients. GI endoscopy revealed signs of congestive and edematous gastritis in patients 2 and 3, and hemorrhagic esogastroduodenitis in patient 1. Pathology confirmed this active gastritis with presence of H. pylori bodies. All patients were kept on anti-acids and prokinetics, and formula was changed to a hydrolysate one in patients 1 and 3. Patient 2 was kept on amino-acid formula, and was given antibiotic therapy (amoxicillin and clarithromycin). Significant improvement and resolution of all symptoms was obtained in all patients. Conclusion: H. pylori infection in neonates is very rare, and clinical presentation can vary from signs of minimal GER to those of gastritis and esophagitis. The role of H. pylori infection on the genesis of CMP intolerance has been reported, but there is no clear consensus on eradication treatment of HP in this age group. We think that combination therapy for both GERD and CMPA should be given when no clinical improvement is rapidly obtained, before deciding on eradication of H. pylori.

O0102 PROTEIN HYDROLYSIS OF INFANT FORMULAS STRONGLY ACTIVATES THE MAILLARD REACTION

Introduction: The particular composition of infant formulas favours the development of the Maillard reaction during processing, inducing nutritional and health hazard effects such as loss of available lysine and promotion of the inflammatory response. Lactose, the main substrate of the reaction in milk, is present at high concentrations. Ascorbate and polyunsaturated fatty acids are oxidable nutrients which give rise upon heat treatment to many other reactive dicarbonyle substrates. These substrates attack the free amino groups of proteins, mainly the e-NH2 group of lysine in milk proteins. Hydrolysis of the proteins induces a tremendous increase of the reactive amino groups, via the terminal a-NH2 of peptides or free amino-acids. The aim of this study is to evaluate the effect of protein hydrolysis on the Maillard reaction in the formula. Four indicators were selected to estimate the nutritional quality and safety of infant formulas. Methods: Hydrolyzed and non hydrolyzed formulas processed as powders or sterilized liquids were purchased from the market (Germany and France). Furosine and free hydroxymethylfurfural were quantified by HPLC-UV; carboxymethyllysine (CML) was estimated by ELISA and fluorescent Maillard products (FMP) were measured directly on the powders or liquid samples by front-face fluorescence. These indicators were also measured on samples stored at 60°C for 4–7 days, to mimic long storage. Results: Hydrolysis of the proteins strongly (2 to 3 times) increased the furosine and CML contents of the formulas. Similarly, FMP were significantly higher indicating that protein hydrolysis is an important parameter for the rate of development of the Maillard reaction. The type of process also had a significant effect, as powders were less altered than sterilized liquid formulas. However, accelerated aging had a much stronger effect on powders, especially when the water content was higher than 6 %. Conclusion: Protein hydrolysis is proposed to decrease the allergenicity to milk proteins. However, the liberation of free reactive amino-groups strongly increases the Maillard reaction with possible nutritional and safety consequences. Milder heat treatments for drying and sterilizing should limit the extent of the Mail-lard reaction.

Development of childhood asthma and formula milk

The aim of this article is to estimate the effect of dietary avoidance of standard cows milk protein on the development of asthma and/or wheeze in infants with a family history of atopy using a systematic review of all available randomized controlled trials. Eleven trials were included in the review. The results show that risk of infants experiencing asthma or wheeze during the first year of life was reduced when using hydrolysed milk formula instead of standard cow's milk formula. Use of soya-based formulas did not reduce the risk of having asthma or wheeze. This article concludes that breastfeeding should be the treatment of choice for all babies. However, where supplemental feeding is required, hydrolysed formula (in combination with dietary restrictions and reduction in environmental allergen exposure) significantly reduces the risk of developing asthma or wheeze in the first year of life in infants with a family history of atopy. Currently, there is insufficient evidence to suggest that soya-based milk formula modifies the risk of developing asthma or wheeze.

Nutritional evaluation of protein hydrolysate formulas in healthy term infants: plasma amino acids, hematology, and trace elements

Protein hydrolysate formulas are used for infants with food allergy. Most studies of such formulas focus on their effect on allergy and rarely evaluate their capacity to provide normal nutritional status. We compared plasma aminograms, serum urea nitrogen, and trace element status in breastfed infants, infants fed hydrolysate formulas, and infants fed milk formula. From 6 wk to 6 mo of age, infants were breastfed or fed regular milk formula (RF), 1 of 2 casein-hydrolysate formulas (CH-1 or CH-2), or whey-hydrolysate formula (WH). Anthropometric measures were taken monthly, and blood samples were collected at 6 wk and 6 mo. Plasma amino acids, serum urea nitrogen, hematologic indexes, plasma zinc, and plasma copper were analyzed. There were no significant differences in hemoglobin, serum transferrin receptor, copper, or zinc among groups. Serum ferritin was significantly lower in infants fed the CH formulas than in the other groups. Infants fed CH-2 had significantly higher serum urea nitrogen than did all other groups. Plasma threonine, valine, phenylalanine, methionine, and tryptophan were significantly higher in the hydrolysate formula groups than in the breastfed group. Plasma tyrosine was significantly lower in infants fed the CH formulas than in the breastfed group, whereas arginine was significantly higher in the WH group than in all other groups. Plasma proline was lower, whereas threonine and tryptophan were higher, in the WH group than in the CH groups. The iron status of infants fed CH formula was lower than that of all other groups. The amounts of amino acids provided by hydrolysate formulas appear excessive compared with regular formula, which is reflected by high serum urea nitrogen (CH-2) and high plasma amino acid concentrations. A reduced and more balanced amino acid content of hydrolysate formulas may be beneficial.

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.

Allergenicity of a hydrolyzed rice infant formula in a guinea pig model

Because sensitization to cow's milk is a common finding in children, the identification of safe alternative protein sources is important in the management of childhood allergy. To evaluate, in an animal model, the allergenicity of a novel formula based on hydrolyzed rice proteins. We conducted an experiment involving 130 guinea pigs, from 7 to 12 days old at the onset of the study. The animals were divided into 13 groups and were given, ad libitum, one of the following liquids to drink: (1) rice hydrolysate formula (RF), (2) a conventional cow's milk formula (CMF), or (3) water. After a 37-day sensitization period, a challenge was given, consisting of an intravenous injection of either isolated proteins or ultracentrifuged formulas (uCMF and uRF). Specific IgG antibodies to beta-lactoglobulin, casein, and whole rice protein were measured by enzyme-linked immunosorbent assay. When animals fed CMF were challenged with beta-lactoglobulin, casein, or whole uCMF, they showed significantly more reactions than did those fed RF when challenged with the same proteins (P < 0.001). In the groups fed RF, no reaction was observed after challenge with uRF, and only 2 mild reactions occurred after challenge with rice protein. Very low levels of specific IgG antibodies to rice protein were noted in all the groups, including the RF-fed animals, and no significant differences were evident between groups. The findings suggest that this new formula based on hydrolyzed rice proteins has a very low sensitizing capability.