Hydrolyzed Formula for Every Infant?

Presently, hydrolyzed formulas (HF) are used primarily in infants that cannot be exclusively breastfed, those with cow's milk allergy and for primary prevention of allergic disease, but HFs are increasingly being used worldwide, begging the question if they may be recommended as the optimal choice for all standard-risk, full-term, non-exclusively breastfed infants. Data regarding the nutritional adequacy of modern-day HFs are scarce and lack long-term data suggesting that growth in infants fed HF versus an intact protein formula (IPF) is different. While human breast milk is the optimal source of nutrition for multiple reasons, a 2006 systematic review determined there were no comparable long-term studies regarding prolonged use of HFs versus breastfeeding. Meta-analyses of formula consumption and risk of atopic dermatitis (AD) have found that infants fed partially HF compared to IPF had a lower risk of AD, but there are significant limitations to these studies, making conclusions about the general use of HFs problematic. Costs should be considered in decision-making regarding the choice of the formula, but global comparison of this is difficult given large cost differences in different countries. Despite the issues raised here, the desire to provide concrete recommendations of widespread HF use needs to be balanced carefully in order not to overstate claims of benefit. Long-term studies are needed to investigate the feasibility of HF as a routine feeding option for healthy, standard-risk infants. Because of the paucity of data, routine use of HF as an equivalent option to breastfeeding or IPF cannot be supported at present based on available scientific evidence.

Clinical and follow up assessment of children in a program directed at the use of formulas for cow's milk protein allergy.

OBJECTIVE: To determine clinical and follow up characteristics of children enrolled in a program to supply formulas for cow's milk allergy. METHODS: descriptive study of a convenience sample composed of 214 children up to three years old, with clinical diagnosis of cow's milk allergy and/or standardized oral challenge, referred to the Program of Formulas for Cow's Milk Allergy at a Pediatric University Hospital, in Natal, Rio Grande do Norte, Brazil (2007/2009). Clinical-epidemiological data and formula indication (soy, protein hydrolysates or aminoacid formula) were assessed at the first consultation. Clinical response and nutritional evolution (Anthro-OMS2006) were observed after three months. Chi-square and paired t-test were used, being p<0.05 significant. RESULTS: At the first consultation, mean age was 9.0±6.9 months. Digestive manifestations occurred in 81.8%; cutaneous ones, in 36.9% and respiratory ones in 23.8%. BMI Z-score <-2.0 standard deviations (SD) was found in 17.9% of children with isolated digestive symptoms, in 41.7% of those using cow's milk and in 8.7% of those using other formulas (p<0.01). The following formulas were used: soy in 61.2%, protein hydrolysates in 35.4% and aminoacids in 3.3%. Mean BMI Z-scores at initial consultation and after three months were, respectively: -0.24±1.47SD and 0.00±1.26SD (p=0.251), with soy formula, and -0.70±1.51SD and -0.14±1.36SD (p=0.322) with protein hydrolysates formula. CONCLUSIONS: Digestive manifestations of cow's milk allergy were preponderant, and lead to greater nutritional impairment. The use of replacement formulas (isolated soy protein and protein hydrolysates) was important to maintain the nutritional status.

Avaliação clínica e evolutiva de crianças em programa de atendimento ao uso de fórmulas para alergia à proteína do leite de vaca / Clinical and follow up assessment of children in a program directed at the use of formulas for cow's milk protein allergy / Evaluación clínica y evolutiva de niños en programas de atención al uso de fórmulas para alergia a la proteína de leche de vaca

OBJETIVO: Determinar características clínicas e evolutivas de crianças acompanhadas em programa de referência para fornecimento de fórmulas especiais para alergia ao leite de vaca. MÉTODOS: Estudo descritivo, realizado em amostra de conveniência, com 214 crianças até três anos, com diagnóstico clínico e/ou teste padronizado de provocação oral aberto, referenciadas ao Programa de Fórmulas para Alergia ao Leite de Vaca, em Hospital Universitário Pediátrico de Natal, Rio Grande do Norte (2007/2009). Avaliaram-se dados clínico-epidemiológicos e indicação de fórmulas (soja, hidrolisado ou aminoácido) à consulta inicial, além de resposta clínica e evolução nutricional (Anthro-OMS 2006) após três meses. Aplicaram-se os testes do qui-quadrado e t pareado nas análises, considerando-se significante p<0,05. RESULTADOS: Ao primeiro atendimento, a média de idade foi de 9,0±6,9 meses. Manifestações digestórias foram observadas em 81,8%; cutâneas, em 36,9%; e respiratórias, em 23,8%. Escore Z do IMC <-2,0 desvios padrão (DP) foi encontrado em 17,9% das crianças com sintomas digestórios isolados, em 41,7% em uso de leite de vaca e em 8,7% com outras fórmulas (p<0,01). Fórmula de proteína isolada de soja foi usada em 61,2%; hidrolisados, em 35,4%; e aminoácidos, em 3,3%. As médias de escore Z do IMC ao atendimento inicial e após três meses foram, respectivamente, -0,24±1,47DP e 0,00±1,26DP (p=0,251), quando em uso de soja, e -0,70±1,51DP e -0,14±1,36DP (p=0,322), em uso de hidrolisado. CONCLUSÕES: Manifestações digestórias da alergia ao leite de vaca foram preponderantes e determinaram maior comprometimento nutricional. As fórmulas de substituição ao leite de vaca mais utilizadas foram de proteína isolada de soja e hidrolisados proteicos. O uso de ambas foi importante para a manutenção do estado nutricional.

OBJECTIVE: To determine clinical and follow up characteristics of children enrolled in a program to supply formulas for cow's milk allergy. METHODS: descriptive study of a convenience sample composed of 214 children up to three years old, with clinical diagnosis of cow's milk allergy and/or standardized oral challenge, referred to the Program of Formulas for Cow's Milk Allergy at a Pediatric University Hospital, in Natal, Rio Grande do Norte, Brazil (2007/2009). Clinical-epidemiological data and formula indication (soy, protein hydrolysates or aminoacid formula) were assessed at the first consultation. Clinical response and nutritional evolution (Anthro-OMS2006) were observed after three months. Chi-square and paired t-test were used, being p<0.05 significant. RESULTS: At the first consultation, mean age was 9.0±6.9 months. Digestive manifestations occurred in 81.8%; cutaneous ones, in 36.9% and respiratory ones in 23.8%. BMI Z-score <-2.0 standard deviations (SD) was found in 17.9% of children with isolated digestive symptoms, in 41.7% of those using cow's milk and in 8.7% of those using other formulas (p<0.01). The following formulas were used: soy in 61.2%, protein hydrolysates in 35.4% and aminoacids in 3.3%. Mean BMI Z-scores at initial consultation and after three months were, respectively: -0.24±1.47SD and 0.00±1.26SD (p=0.251), with soy formula, and -0.70±1.51SD and -0.14±1.36SD (p=0.322) with protein hydrolysates formula. CONCLUSIONS: Digestive manifestations of cow's milk allergy were preponderant, and lead to greater nutritional impairment. The use of replacement formulas (isolated soy protein and protein hydrolysates) was important to maintain the nutritional status.

OBJETIVO: Determinar características clínicas y evolutivas de niños acompañados en programa de referencia para suministro de fórmulas especiales para alergia a la leche de vaca. MÉTODOS: Estudio descriptivo, realizado en muestra de conveniencia, con 214 niños hasta tres años de edad, con diagnóstico clínico y/o prueba estandarizada de provocación oral abierta, referenciadas al Programa de Fórmulas para Alergia a la Leche de Vaca del Hospital Universitario Pediátrico en Natal, RN, Brasil (2007/2009). Se evaluaron datos clínico-epidemiológicos e indicación de fórmulas (soja, hidrolizado o aminoácido) a la consulta inicial, respuesta clínica y evolución nutricional (Anthro-OMS 2006) después de tres meses. Se aplicaron pruebas de Chi-Cuadrado y T Pareada en los análisis, siendo significante p<0,05. RESULTADOS: A la primera atención, el promedio de edad fue de 9,0±6,9 meses. Manifestaciones digestorias fueron observadas en 81,8%, cutáneas en el 36,9% y respiratorias en el 23,8%. Escore Z IMC<-2,0DE fue encontrado en 17,9% de los niños con síntomas digestorios aislados, en el 41,7% en uso de leche de vaca y en 8,7% en otras fórmulas (p<0,01). Se utilizó fórmula de proteína aislada de soja en 61,2%, hidrolizados en 35,4% y aminoácidos en 3,3%. Promedios de Escore Z IMC a la atención inicial y después de tres meses fueron -0,24±1,47DE y 0,00±1,26DE (p=0,251), cuando en uso de soja, y 0,70±1,51DE y -0,14±1,36DE (p=0,322), en uso de hidrolizado. CONCLUSIONES: Manifestaciones digestorias de la alergia a la leche de vaca fueron preponderantes y determinaron mayor comprometimiento nutricional. Las fórmulas de sustitución a la leche de vaca más utilizadas fueron de proteína aislada de soja e hidrolizados proteicos y el uso de ambas fue importante para el mantenimiento del estado nutricional.

Diagnostic approach and management of cow's-milk protein allergy in infants and children: ESPGHAN GI Committee practical guidelines.

OBJECTIVES: This guideline provides recommendations for the diagnosis and management of suspected cow's-milk protein allergy (CMPA) in Europe. It presents a practical approach with a diagnostic algorithm and is based on recently published evidence-based guidelines on CMPA. DIAGNOSIS: If CMPA is suspected by history and examination, then strict allergen avoidance is initiated. In certain circumstances (eg, a clear history of immediate symptoms, a life-threatening reaction with a positive test for CMP-specific IgE), the diagnosis can be made without a milk challenge. In all other circumstances, a controlled oral food challenge (open or blind) under medical supervision is required to confirm or exclude the diagnosis of CMPA. TREATMENT: In breast-fed infants, the mother should start a strict CMP-free diet. Non-breast-fed infants with confirmed CMPA should receive an extensively hydrolyzed protein-based formula with proven efficacy in appropriate clinical trials; amino acids-based formulae are reserved for certain situations. Soy protein formula, if tolerated, is an option beyond 6 months of age. Nutritional counseling and regular monitoring of growth are mandatory in all age groups requiring CMP exclusion. REEVALUATION: Patients should be reevaluated every 6 to 12 months to assess whether they have developed tolerance to CMP. This is achieved in >75% by 3 years of age and >90% by 6 years of age. Inappropriate or overly long dietary eliminations should be avoided. Such restrictions may impair the quality of life of both child and family, induce improper growth, and incur unnecessary health care costs.

Cost-effectiveness of using an extensively hydrolysed formula compared to an amino acid formula as first-line treatment for cow milk allergy in the UK.

OBJECTIVE: To estimate the cost-effectiveness of using an extensively hydrolysed formula (eHF; Nutramigen) compared with an amino acid formula (AAF; Neocate) as first-line treatment for cow milk allergy (CMA) in the UK, from the perspective of the National Health Service (NHS). METHOD: A decision model was constructed depicting the treatment paths and associated resource use attributable to first-line management of CMA with the two formulae. The model was based on the case records of 145 AAF-treated infants and 150 matched eHF-treated patients from The Health Improvement Network (THIN) database [a nationally representative database of patients registered with general practitioners (GPs) in the UK]. The model estimated the costs and consequences of patient management over 12 months following their initial GP visit for CMA. RESULTS: Patients presenting with a combination of gastrointestinal symptoms and eczema accounted for 44% of all patients in both groups. Those with gastrointestinal symptoms alone and eczema alone accounted for up to a further 39% and 13%, respectively. Those with urticaria and faltering growth accounted for <5% and ≤6% of all patients, respectively. Patients' age and weight at presentation was a mean 2.6-2.8 months and 4.4 kg, respectively. It took a mean 2.2 months to start a formula after initially seeing a GP. Time to symptom resolution following the start of treatment was 1.2 months in both groups; hence, the mean number of symptom-free months during the 12 months following the initial GP visit was estimated to be 8.6 months in both groups. Patients treated with an eHF had a mean 13.1 GP visits over the 12 months compared to 17.5 visits made by AAF-treated patients (p < 0.001). The NHS cost of managing a CMA infant over the first 12 months following initial presentation to a GP was estimated to be £1853 and £3161 for an eHF-treated and AAF-treated patient, respectively. CONCLUSION: Starting treatment for CMA with an eHF was the cost-effective option, as there were no significant differences in clinical outcomes between the two groups. A prospective, randomized controlled trial would allow a definitive confirmation of these findings.

Allergy assessment in children with eosinophilic esophagitis.

BACKGROUND: Eosinophilic esophagitis (EoE) is of growing interest for pediatricians and allergists. There is no general agreement about diagnostic and clinical management procedures. The objective of this prospective, observational study was to evaluate the efficacy of a protocol for the etiologic diagnosis and accurate treatment of EoE in the pediatric population. PATIENTS AND METHODS: Starting in 2001, patients aged 0 to 14 years with a diagnosis of EoE were consecutively included in a protocol which included an allergy study. Depending on the results, an avoidance or elemental diet was established. Topical corticosteroids were prescribed to patients who rejected the diet. Clinical, endoscopic, and histological evaluation was performed to assess response. In the case of disease remission, challenge tests were performed to identify the offending food. RESULTS: Seventeen patients were included. Most of them were male (14/17) and a high percentage (88%) had a history of allergy as well as a history of atopy in parents. Fifteen patients were sensitized to 1 or more foods. With this protocol and the subsequent treatment, 9 out of 17 patients were cured (1 out of 4 with swallowed corticosteroids, 3 out of 3 with an elemental diet, and 5 out of 12 with an avoidance diet). The offending food was identified in 8117 patients. Milk and eggs were the most common foods implicated. CONCLUSIONS: The allergy study was a useful diagnostic tool but it was not sufficient to identify the offending food.An elemental diet should be attempted before food is excluded as the cause of the disease.

Budget impact of managing cow milk allergy in the Netherlands.

OBJECTIVE: To assess the resource implications and budget impact of managing cow milk allergy (CMA) in the Netherlands from the perspective of the healthcare insurers. METHODS: A model was constructed depicting the management of CMA in the Netherlands using information obtained from interviews with youth healthcare doctors (n = 14), general practitioners (n = 6) and paediatricians (n = 11) with relevant clinical experience of managing CMA. The model was used to estimate the expected level of healthcare resource use and corresponding cost (at 2007/08 prices) attributable to managing 4,382 new CMA sufferers. RESULTS: The expected cost of healthcare resource use attributable to managing 4,382 new CMA sufferers up to 1 year of age following initial consultation with a community-based physician at a mean 3 months of age was estimated to be €11.28 (95% CI: €7.82; €14.33) million. Clinical nutrition preparations emerged as the primary cost driver accounting for 91% of the total cost and clinician visits collectively accounted for a further 5%. The time taken for CMA sufferers to be put on an appropriate diet and achieve symptom resolution was estimated to be 30 (95% CI: 27; 32) days. Sensitivity analysis showed that the costs would increase by approximately 16% if all new CMA sufferers were to undergo a double-blind placebo-controlled cow milk challenge in a hospital setting, as is currently being proposed. It is not clear how this proposal would affect time to symptom resolution since this would depend on the efficiency of hospitals being able to deal with the increased workload. LIMITATIONS: The intolerance rates were derived from a 1-year follow-up study among 1,000 infants with CMA in the UK, healthcare resource use was not collected prospectively and the study period was censured at 1 year of age and does not consider the impact of CMA in subsequent years. However, most children outgrow this form of allergy during their second year. CONCLUSION: Within the model's limitations, CMA imposes a substantial burden on the Dutch healthcare system. Moreover, initiating a double-blind placebo-controlled cow milk challenge for all CMA sufferers will potentially increase clinicians' workload and use of limited resources within paediatric hospital departments in the Netherlands.

Modelling the health economic impact of managing cow milk allergy in South Africa.

OBJECTIVE: To quantify the health economic impact of managing cow milk allergy (CMA) in South Africa, from the perspective of healthcare insurers in both the private and public sectors and parents/carers of CMA sufferers. METHODS: A decision model depicting the management of CMA in South Africa was constructed, using information obtained from interviews with paediatric specialists in the private and public sectors with relevant clinical experience. The model was used to estimate the expected 12-monthly levels of healthcare resource use and corresponding costs (at 2007/08 prices) attributable to managing CMA sufferers following an initial consultation with a paediatrician. RESULTS: The expected 12-monthly cost incurred by an insurer attributable to managing a CMA sufferer following an initial consultation with a paediatrician was estimated to be R2,430.4 (€202.0) and R1,073.7 (€89.0) in the private and public sector, respectively. The expected 12-monthly cost incurred by parents/carers following an initial consultation with a paediatrician was estimated to be R43,563.1 (€3,634.0) and R24,899.9 (€2,076.9) in the private and public sector, respectively. The time taken for a CMA sufferer to be put on an appropriate diet and achieve symptom resolution was estimated to be 24 days in the private sector and 18 days in the public sector. The total cost to manage an annual cohort of 18,270 newly diagnosed infants with CMA in South Africa in the first year following presentation to a paediatrician was estimated to be R22.1 (€1.8) million for healthcare insurers and R489.1 (€40.8) million for parents/carers. The expected costs to insurers were driven by visits to general paediatricians and prescriptions for dermatological drugs in both the private and public sectors. The expected costs to parents/carers were driven by over-the-counter (OTC) purchases of clinical nutrition preparations. LIMITATIONS: The intolerance rates were derived from a study among 1,000 infants with CMA in the UK, healthcare resource use was not collected prospectively and the study period was limited to 1 year following presentation to a paediatrician and does not consider the impact of CMA in subsequent years. However, most children outgrow this form of allergy by the time they reach 2 years of age. CONCLUSION: CMA imposes a substantial socio-economic burden in South Africa, especially on parents/carers of CMA sufferers. Any strategy that reduces this burden should potentially lead to higher compliance with clinicians' recommendations, thereby improving health outcomes associated with treatment and should also release healthcare resource use for alternative use.

A murine model of cow's milk protein-induced allergic reaction: use for safety assessment of hidden milk allergens.

BACKGROUND: Masked allergens in processed food products can lead to severe allergic reactions following unintentional ingestion. We sought to develop a murine model for the detection of hidden cow's milk proteins (CMP). This study aimed to induce cow's milk allergy in mice, to characterize the anaphylaxis induced by CMP in this model, and to validate its reliability using three margarines manufactured with (A) or without (B, C) milk, sharing the same production line. MATERIALS AND METHODS: Three-week-old BALB/c mice were sensitized intragastrically with CMP plus cholera toxin and boosted 6 times at weekly intervals. CMP-sensitization status was monitored by skin tests, and measurement of CMP-specific IgE and IgG1 levels. On day 44, the minimal threshold of clinical reactivity to CMP in terms of anaphylaxis was determined by performing a dose response of intraperitoneal CMP challenge. Under the same conditions, anaphylaxis was evaluated in CMP-sensitized mice after challenge with protein extracts of margarines A, B or C. RESULTS: Sensitization to CMP was demonstrated by positive skin tests and increased CMP-specific IgE and IgG1. The minimal clinical reactivity threshold corresponding to 0.1 mg CMP elicited detectable anaphylaxis evidenced by clinical symptoms, a decrease in breathing frequency, and increased plasma histamine upon challenge. Similarly, challenges with margarine A containing CMP demonstrated anaphylaxis, whereas those with B or C did not elicit any detectable allergic reaction. CONCLUSION: This study shows that our murine model of CMP-induced anaphylaxis is useful for investigating the allergenic activity and the assessment of margarines with respect to milk.

Milk allergy school: nutritional therapy in group for parents of children with cow's milk allergy/intolerance in Primary Health Care.

The objective of this study was to create a method for group nutritional therapy for parents of children with cow's milk allergy/intolerance in a paediatric primary care setting to increase accessibility to nutritional therapy. A second objective was to evaluate a milk allergy school. Follow-up time after the group session was 3 yr. All parents to newly diagnosed children (n=98) with cow's milk allergy/intolerance in the Primary Health Care system in the city of Goteborg during an 11-month period were invited. The majority of the families chose to participate (n=84, 86%). The mean age of the children was 9 months (3 months to 5 yr). The number of participants obtaining nutritional treatment within a month after diagnosis has significantly increased. Seventy-four families (88%) could be re-contacted 3 yr after participation for a second evaluation. Seventy-eight per cent of the children no longer had cow's milk allergy/intolerance. Most participants expressed satisfaction with the information obtained in the meeting. The milk allergy school does not replace but complements individual counselling. The milk allergy school seems to meet the families' needs for information, has few administrative routines and is cost-efficient. This activity has become permanent, is being offered weekly and can be recommended.

[Somatic development assessment of children with food allergy treated with milk free diet]. / Ocena rozwoju somatycznego dzieci z alergia pokarmowa leczonych diet a eliminacyjna.

The aim of our study was to evaluate the influence of one year elimination diets on the somatic development and the nutritional status of children. 25 patients from the Department of Immunology of the Institute of Mother and Child aged 1-7 years with cow's milk allergy were investigated. The children were divided into two groups: 10 children received hydrolizated casein formula and 15 children received soya protein formula. The somatic development and nutritional status was assessed twice, the first time before the onset of treatment and the second time after one year of treatment. Anthropometric methods were used, body height, body mass, upper arm circumference and subscapular skinfold were measured. The data were compared with the normal Warsaw population data from 1996-99. The results showed that both the diet with hydrolizated casein formula and the soya protein resulted in normal somatic development of children.