Effect of maternal immune level at different pregnancy stages on cow's milk protein allergy in infants / 中国当代儿科杂志

OBJECTIVE@#To study the association between maternal Th1/Th2 immune level at different pregnancy stages and cow's milk protein allergy (CMPA) in infants.@*METHODS@#The healthy women with a singleton pregnancy, as well as their offspring, who attended Yidu Central Hospital of Weifang and Qingzhou Traditional Chinese Medicine Hospital from July 2016 to December 2018 were enrolled. The maternal levels of interleukin-2 (IL-2), interferon gamma (IFN-γ), interleukin-4 (IL-4), and interleukin-10 (IL-10) at the second and third trimesters of pregnancy were measured. A CMPA questionnaire survey was conducted within one year after birth. Food avoidance and cow's milk oral challenge tests were performed in infants suspected of CMPA. The 48 infants who met the diagnostic criteria for CMPA were included in the observation group, and the remaining 977 normal infants were included in the control group. A univariate analysis was performed on the infants with CMPA. A Poisson regression analysis was used to determine the association between maternal Th1/Th2 immune factors at different pregnancy stages and CMPA.@*RESULTS@#The detection rate of CMPA was 4.68%. The clinical manifestations included the symptoms of the digestive system, skin, and respiratory system and other symptoms. The univariate analysis showed that compared with the control group, the observation group had significantly higher incidence rates of maternal food allergy and maternal history of allergic diseases (P<0.05) and a significantly lower breastfeeding rate (P<0.05). The observation group had significantly lower maternal levels of IL-2 (second and third trimesters) and IFN-γ (third trimester) than the control group (P<0.05). Maternal low IFN-γ at the third trimester and maternal low IL-2 at the second and third trimesters were significantly associated with CMPA in infants (P<0.05). After correction of the factors of breastfeeding, maternal food allergy, and maternal history of allergic diseases, it was found that maternal low IL-2 and IFN-γ at the third trimester were still significantly associated with CMPA in infants (P<0.05).@*CONCLUSIONS@#The maternal decrease in Th1 level at the third trimester of pregnancy may lead to the change in fetal immunity and thus increase the risk of CMPA in offspring.

Actualización en manejo de alergia a la proteína de leche de vaca: fórmulas lácteas disponibles y otros brebajes / Update on management of cow's milk protein allergy: available milk formulas and other juices

La alergia a la proteína de leche de vaca (APLV) es una enfermedad frecuente, con una prevalencia entre 2-7%, cifras que van en aumento. Se caracteriza por una reacción alérgica a una o más pro teínas de la leche de vaca. No existen manifestaciones clínicas patognomónicas, y éstas dependerán del tipo de reacción inmunológica involucrada. Una buena aproximación diagnóstica evita el sub y sobre diagnóstico y por lo tanto, sub y sobre tratamiento. El tratamiento de la APLV es la eliminación de la proteína de leche de vaca de la dieta. Una dieta de restricción en un niño que no la requiere o que ha desarrollado tolerancia, puede alterar el crecimiento, la calidad de vida y producir costos innecesarios. El objetivo de esta actualización es presentar las diferentes fórmulas y brebajes usados en Chile para tratar la APLV en aquellos casos en que no sea posible la lactancia materna con dieta de exclusión. Para ello se revisó la composición nutricional, ingredientes y otras características relevan tes de todas aquellas fórmulas o brebajes que se comercializan en Chile como tratamiento de APLV. La información se obtuvo desde los distribuidores o vendedores oficiales, o en su defecto, desde las páginas web oficiales. Se puede concluir que existen y se usan múltiples fórmulas y brebajes para el tratamiento de APLV, no todas ellas del todo adecuadas desde el punto de vista nutricional y de seguridad. Conocerlas en detalle ayudará al pediatra a indicarlas de manera más informada de acuerdo a sus beneficios y sus carencias para el manejo adecuado de esta patología.

Cow's milk protein allergy (CMPA) is a common disease with a prevalence of 2-7%, increasingly so. It is characterized by an allergic reaction to one or more cow's milk proteins. There are not pathog nomonic clinical symptoms, and these will depend on the type of immune reaction involved. A good diagnostic approach avoids under and over diagnosis and, therefore, under and over treatment. The CMPA treatment is the elimination of cow's milk protein from the diet. A restricted diet in a child does not require it or who has developed tolerance can alter growth, quality of life, including unne cessary costs. The objective of this review is to present the different milk formulas available in Chile to treat CMPA in those cases where breastfeeding with exclusion diet is not possible. For this purpose, nutritional composition, ingredients and other relevant characteristics of all the milk formulas and juices marketed in Chile as CMPA treatment were reviewed. The information was obtained from the official distributors or sellers or failing that, from the official websites. There are multiple milk formulas and beverages used for the treatment of CMPA, and not all of them are nutritionally or immunologically secure. Knowing them in detail will help the pediatrician to indicate them in a more informed way according to their benefits and their deficiencies for the proper management of this pathology.

Caries in children with lactose intolerance and cow's milk protein allergy

Abstract Dental caries in 5-to-8-year-old children with cow's milk protein allergy (CMPA) and lactose intolerance (LI), their treatment needs, and the consumption of milk-based products and milk derivatives by these patients were investigated. A cross-sectional study was undertaken with 200 children in southern Brazil in 2017. The clinical examination was based on the World Health Organization criteria and a questionnaire was sent to parents or legal guardians to collect information on the children's food intake, pre-existing systemic diseases, medication use, and CMPA and LI. Standardization was performed to verify concordance among examiners (kappa = 0.96). Caries prevalence was 67.50% in children with CMPA or LI, but 34.37% in those without these conditions. The mean dmft (decayed, missing, and filled teeth) index in children with CMPA or LI was 1.75 ± 1.84, significantly higher than among non-allergic or lactose-tolerant children (0.83 ± 1.60) (p < 0.001). In children with CMPA or LI, the mean for treatment needs was 1.58 ± 1.50. Lactose-free milk was the most frequently consumed food among allergic/intolerant children (65.00%), with a mean dmft of 2.00 ± 2.08, higher than that obtained for those without CMPA/LI (0.82 ± 0.87), showing no significant difference (p = 0.129). Although dental caries and treatment needs in primary dentition were associated with CMPA or LI, children's intake of replacement foods did not pose any risk for the development of carious lesions. Statistically significant differences were obtained for the prevalence and severity of dental caries. This shows the need for treatment of children with CMPA or LI, who had the worst caries prevalence and severity rates.

Proteomics: a tool to develop novel diagnostic methods and unravel molecular mechanisms of pediatric diseases / Proteómica: una herramienta para desarrollar nuevos métodos de diagnóstico y descifrar mecanismos moleculares de enfermedades pediátricas

Abstract: Proteomics is the study of the expression of changes and post-translational modifications (PTM) of proteins along a metabolic condition either normal or pathological. In the field of health, proteomics allows obtaining valuable data for treatment, diagnosis or pathophysiological mechanisms of different illnesses. To illustrate the aforementioned, we describe two projects currently being performed at the Instituto Nacional de Pediatría: The immuno-proteomic study of cow milk allergy and the Proteomic study of childhood cataract. Cow's milk proteins (CMP) are the first antigens to which infants are exposed and generate allergy in some of them. In Mexico, the incidence of CMP allergy has been estimated at 5-7%. Clinical manifestations include both gastrointestinal and extra-gastrointestinal symptoms, making its diagnosis extremely difficult. An inappropriate diagnosis affects the development and growth of children. The goals of the study are to identify the main immune-reactive CMP in Mexican pediatric population and to design more accurate diagnostic tools for this disease. Childhood cataract is a major ocular disease representing one of the main causes of blindness in infants; in developing countries, this disease promotes up to 27% of cases related to visual loss. From this group, it has been estimated that close to 60% of children do not survive beyond two years after vision lost. PTM have been pointed out as the main cause of protein precipitation at the crystalline and, consequently, clouding of this tissue. The study of childhood cataract represents an outstanding opportunity to identify the PTM associated to the cataract-genesis process.

Resumen: La proteómica estudia los cambios de expresión y post-traduccionales (PTM) de las proteínas durante una condición metabólica normal o patológica. En el campo de la salud, la proteómica permite obtener datos útiles para el tratamiento, diagnóstico o en la fisiopatología de diferentes enfermedades. Para ilustrar lo anterior, describimos dos proyectos realizados en el Instituto Nacional de Pediatría: El estudio inmunoproteómico de la alergia a la leche y el estudio proteómico de la catarata infantil. Las proteínas de leche bovina (PLB) son los primeros antígenos a los que se exponen los infantes y un porcentaje de ellos generará alergias. En México, se estima que la incidencia de alergias a las PLB es del 5-7%. Las manifestaciones clínicas incluyen tanto síntomas gastrointestinales como extra-gastrointestinales, dificultando su diagnóstico. Un mal diagnóstico afecta el desarrollo y crecimiento del infante. Los objetivos del estudio son identificar las principales PLB inmunoreactivas en población infantil mexicana y diseñar herramientas diagnósticas más precisas para esta patología. La catarata infantil es una enfermedad ocular que representa una de las causas principales de ceguera infantil; en países subdesarrollados genera cerca del 27% de casos relacionados con pérdida visual. De este grupo, se estima que cerca del 60% de los infantes no sobreviven más allá de los dos años después de perder la visión. Se señala a las PTM como las responsables de la precipitación de proteínas del cristalino y, por tanto, de su opacidad. El estudio de la catarata infantil representa una oportunidad para identificar las PTM vinculadas con la cataratogénesis.

Deposiciones sanguinolentas iniciadas en los primeros días de vida / Bloody stools started in the first days of life

La proctocolitis alérgica del lactante es un trastorno caracterizado por la presencia de deposiciones mucosanguinolentas en los dos primeros meses de vida, pudiendo aparecer en los primeros días de vida. Anteriormente, relacionado con niños alimentados con lactancia artificial, en los últimos años se observa un aumento de la incidencia en niños alimentados con lactancia materna exclusiva debido al paso de proteínas de leche de vaca a la leche de la madre. Recién nacido a término, alimentado con lactancia materna exclusiva inicia a los dos días de vida deposiciones con hebras de sangre de forma intermitente. Todos los estudios realizados resultan normales. La clínica mejora progresivamente tras la eliminación de las proteínas de leche de vaca de la dieta de la madre, por lo que se diagnostica de proctocolitis alérgica. El diagnóstico se basa en la clínica, la desaparición de los síntomas al retirar las proteínas de leche de vaca de la dieta, y en la reaparición de éstos al reintroducirla. Los niños mantienen buen estado general en todo momento, siendo la gran mayoría tolerantes a la leche de vaca al año de vida, por lo que se considera una patología de buen pronóstico.

Allergic colitis is a pathology characterized by blood in faeces, appeared in first two months of life, but it can also appear during the first days of life. Previously it was related with children with non breastfeeding, however in the last years incidence is increasing in children with breastfeeding. This is explained with the presence of cow’s milk proteins in human’s milk. Newborn term, fed with exclusive breastfeeding, starts at second day of life blood in faeces, intermittently. The studies done are normal. The symptoms improve progressively after removing the cow’s milk proteins of the mother’s diet, so the child is diagnosed with allergic protocolitis. Diagnosis is based on the symptoms, the improvement with the removal of the cow’s milk protein of the diet, and the worsening when they are reintroduced. The children conserve good general condition every moment, almost all of them tolerate cow’s milk when they are one year old, and so it is considered pathology of well prognosis.

Características clínicas y manejo de lactantes menores de 1 año con sospecha de alergia a proteína de leche de vaca / Clinical characteristics and management of infants less than 1-year-old suspected with allergy to cow's milk protein

Introducción: La alergia a proteína de leche de vaca (APLV) es frecuente en lactantes (2-5% en < 1 año). Tiene múltiples formas de presentación y un amplio diagnóstico diferencial, por lo que es relevante confirmar el diagnóstico. El estándar de oro del diagnóstico es el test de provocación oral (TPO), que en la práctica no siempre se realiza. En Chile hay escasa literatura respecto a esta entidad. Objetivo: Describir características demográficas, clínicas y manejo de lactantes < 1 año con sospecha de APLV. Pacientes y Método: Estudio retrospectivo en menores de 1 año atendidos por sospecha de APLV entre 2009-2011. Se registraron datos demográficos, historia perinatal, antecedentes de atopia, alimentación al momento del diagnóstico, síntomas de sospecha de APLV, estudios realizados para su confirmación, y respuesta a tratamiento. Se consideró como estándar de diagnóstico la respuesta a la dieta y la contraprueba. Se definió como respuesta a la dieta la ausencia de los síntomas atribuidos a la APLV al menos 4 semanas desde el cambio de leche. Se realizó estadística descriptiva mediante programa Epiinfo™. Resultados: Se incluyeron 106 lactantes, 51% varones, 80% recién nacidos de término, 74% con al menos un progenitor atópico, 34% con alguno de los padres o algún hermano con alergia alimentaria. La mediana de edad al inicio fue 1,5 meses (rango: 1,5-2 m). El 15% recibió fórmula desde el período neonatal y el 50% antes del tercer mes. Los síntomas más frecuentes fueron: vómitos (63%), cólicos (50%) y rectorragia (40%); el 61% presentó ≥ 2 síntomas al comienzo. Solo en el 34% se hizo TPO, en el resto se evaluó la respuesta a la dieta de exclusión y se realizaron exámenes. La realización de exámenes no cambió la conducta. Tratamiento: 43% lactancia materna con dieta de exclusión, 24% solo fórmula extensamente hidrolizada, 26% solo fórmula aminoacídica y 7% otros. Conclusión: Las características demográficas y antecedentes de los pacientes concuerdan con lo descrito en la literatura extranjera. El inicio clínico fue precoz, predominando los síntomas digestivos. Se realizaron exámenes en una proporción alta de pacientes, sin contribuir a un cambio de conducta; el TPO fue subutilizado como herramienta diagnóstica.

Introduction: Cow's milk protein allergy (CMPA) is highly prevalent in infants (2-5%). It has a wide clinical spectrum, and confirmation through an oral food challenge (OFC) is relevant for its differential diagnosis. Information on this topic is scarce in Chile. Objective: To describe the demographic and clinical features of infants with suspected CMPA. Patients and Method: A retrospective study of patients < 1 year-old, treated for suspected CMPA between 2009 and 2011. Demographic data, symptoms of atopy, nutrition at the time of diagnosis, CMPA symptoms, diagnostic studies, and response to treatment were recorded. Diet response at least 4 weeks after milk modification, and clinical behavior when suspected foods were added back to the diet were considered standard diagnostic criteria. Descriptive statistics were performed using Epiinfo ™ software. Results: The study included 106 infants, of whom, 51% male, 80% term newborns, 74% with ≥ 1 atopic parent, and 34% with ≥ 1 parent/sibling with food allergy. The median age at onset of symptoms was 1.5 months (range 1.5-2 m). Almost half (46%) were breast-feeding ≥ 6 m, with 15% receiving formula milk since the neonatal period, and 49% before the third month. Common symptoms were: vomiting (63%), colic (49%), and bleeding on passing stools (41%). No anaphylaxis was identified, and 61% had ≥ 2 symptoms at debut. Only 34% were subjected to OFC. The most frequently requested tests were, test patch (43%), prick test (40%), and blood in stools (37%). Treatment: 43% breast feeding with exclusion diet, 24% extensively hydrolysed formula, 26% amino acid formula, and 7% others. Conclusion: Demographic characteristics and risk factors were similar to those previously described in international literature. Clinical presentation was early in life, and digestive symptoms predominated. OFC was underused for diagnosis, and most of the tests requested did not change management.

Características clínicas asociadas a colitis eosinofílica en lactantes con rectorragia persistente / Clinical features of Eosinophilic Colitis in infants with persistent rectal bleeding

The most common presentation of cow's milk protein allergy (CMP) in infants is known as eosinophilic colitis (EC). The aim of this study is to evaluate EC characteristics in infants evaluated with colonoscopy due to the presence of rectorrhagia. Patients and Methods: A retrospective case-control study. Left-sided colonoscopy records of infants with persistent rectal bleeding, conducted between January 2006 and March 2011, were reviewed. The cases corresponded to infants with rectal biopsy compatible with EC and controls with negative biopsy. Telephone questionnaires to parents were conducted, evaluating personal and family history. Results: Complete records were obtained in 61 (79%) of the 77 procedures. 33 (54%) of them were males. Examination average age was 6.3 ± 5.9 months. 25 (41%) patients had EC on their histology. Between cases and controls, no significant difference in gestational age, birth weight and gender, only regarding age at the time of rectal bleeding, were observed. There was also no difference in personal history regarding obstructive bronchitis, allergic rhinitis, family history of asthma, allergic rhinitis or other food allergies. Those who received artificial feeding did not presented greater risk of EC. The most common symptoms in the cases did not differ significantly from the controls. Conclusions: The prevalence of EC in the children studied was 40.9%. Our results show that there are groups of patients with persistent rectal bleeding in which there is no personal or family history that helps diagnosing EC. An endoscopic study could be considered in these patients to establish a correct diagnosis of this condition, avoid unnecessary diets and not to delay the detection of other diseases.

En lactantes, la forma de presentación más común de la alergia a la proteína de la leche de vaca (PLV) es la colitis eosinofílica (CE). El objetivo de este trabajo es evaluar características clínicas asociadas a CE en lactantes evaluados con colonoscopía por la presencia de rectorragia. Pacientes y Método: Estudio caso-control, retrospectivo. Se revisaron registros de colonoscopía izquierda de lactantes con rectorragia persistente, realizadas entre Enero 2006 y Marzo 2011. Casos fueron lactantes con rectorragia y biopsia compatible con CE y controles aquellos con biopsia negativa. Se realizó un cuestionario vía telefónica a los padres, evaluándose antecedentes personales y familiares. Resultados: En 61 (79%) de 77 procedimientos se obtuvo registros completos. 33 (54%) eran hombres. Edad promedio del examen fue 6,3 ± 5,9 meses. 25 (41%) pacientes presentaron CE en la histología. Sin diferencia significativa en edad gestacional, peso de nacimiento ni sexo, pero si en edad de presentación de la rectorragia, entre casos y controles. Tampoco hubo diferencia en antecedentes personales de bronquitis obstructivas, rinitis alérgica, ni antecedentes familiares de asma, rinitis alérgica u otras alergias alimentarias. Quienes recibieron lactancia artificial no tuvieron mayor riesgo de CE. Los síntomas más frecuentes en los casos no se diferenciaron significativamente de los controles. Conclusión: La prevalencia de CE en los niños estudiados fue de 40,9%. Nuestros resultados muestran que hay grupos de pacientes con rectorragia persistente en los cuales no existen antecedentes de la historia familiar ni personal que permitan establecer el diagnóstico de CE. Es en estos pacientes en los cuales podría considerarse el estudio endoscópico para establecer un correcto diagnóstico de esta patología, evitar dietas innecesarias y no retrasar la detección de otras enfermedades.

[Allergic reaction of goats and cows milk proteins]

Systemic anaphylaxis test in mouse showed that the visual effect of injection of cow casein, whey, casein fraction and bovine beta-lactoglobulin was strong. Similar results were found when goat casein, Kappa-casein and beta-casein were injected. The visual effect of injection of beta-lactoglobulin and alpha[s],-casein was low. No response was found when bovine and goat alpha-Lactalbumin was injected in animals. Passive cutaneous anaphylaxis test in mouse showed that the reaction area of cow casein injection was 0.63 cm[2] in comparison with 0.19 cm[2] for goat casein. The reaction of cow beta-lactoglobulin injection was 0.12 cm[2], while no reaction was occurred when goat beta-lactoglobulin, goat and cow alpha-lactalbumin were injected. The percentage of degranulation of mast cells when treated with cow raw milk, casein, whey, beta-lactoglobulin and alpha-lactalbumin were 32.11, 100, 41.80, 90.01 and 12.73% respectively, In comparison with 14.33, 80.19, 34.73, 39.57 and 10.86% respectively for the same proteins in goat milk

Indexes of Suspicion of Typical Cow's Milk Protein-Induced Enterocolitis

This study was performed to identify clinical factors that facilitate the diagnosis of typical cow's milk protein-induced enterocolitis (CMPIE). Data from 142 consecutive patients (aged 15 to 45 days, cow's milk formula- or cow's milk and breast milk mixed-fed) admitted due to vomiting and/or diarrhea were retrospectively analyzed. These 142 subjects were divided into three groups: the CMPIE, infection, and non-infection group. Each group was composed of 16 (11.3%), 102 (71.8%), and 24 (16.9%) patients, respectively. On admission, poor weight gain (p=0.003), hypoalbuminemia (p=0.035), peripheral leukocytosis (p=0.012), and metabolic acidosis (p=0.015) were found to be more significant in the CMPIE group than those in other two groups. In CMPIE, serum albumin levels decreased from 3.3+/-0.9 g/dL on admission to 2.6+/-0.3 g/dL during admission (p<0.05), and methemoglobinemia was observed in 3 patients (18.8%) (p=0.012). Multiple logistic regression analysis showed that the independent predictors of CMPIE versus the infection group were failure to gain weight (OR, 10.75 [95% CI, 1.53-66.12]) (p= 0.014) and hypoalbuminemia (OR, 9.53 [95% CI, 1.62-49.01]) (p=0.010). The early recognition of indexes of suspicion for CMPIE may be of help in the diagnosis and treatment of this disorder.

Utilizaçäo do leite de cabra em crianças com alergia ao leite de vaca / Use of goat's milk in children with cow's milk allergy

O leite de cabra tem sido utilizado com muita freqüência no tratamento de crianças com alergia ao leite de vaca. Neste artigo, mostraremos as semelhanças entre esses leites e a ausência de respaldo científico para a utilizaçäo do leite de cabra nessas crianças

Proteínas de la leche y su asociación con diabetes mellitus insulino-dependiente / Milk proteins and it association with insulin dependent diabetes mellitus

Cow`s milk has been implicated as a possible trigger of the autoinmune respose that destroys pancreatic beta cells in genetically susceptible host, thus causing diabetes mellitus. Studies in animals have suggested that bovine serum albumin, BSA, is the milk protein responsible, and an albumin peptide containing 17 amino acids, ABBOS, may be the reactive epitope. Antibodies to this peptide react with p69 a beta cell surface protein that may represent the target antigen for milk-induced beta-cell specific inmunity. The consumption of cow`s milk in Europe may support the hypothesis that cow`s milk may be a triggering factor for the development of type I diabetes. However, several epidemiological studies has not found significance correlation between the observed the importance of several enviromental factors in the devepment of type I diabetes with the objetive to establish a good prevention in susceptible subjects