Tratamiento de la alergia a la proteína de la leche de vaca. Consenso interdisciplinario de expertos / Cow's milk allergy treatment. An expert consensus

El tratamiento de la alergia a las proteínas de la leche de vaca se basa en la eliminación completa de las proteínas de leche de vaca de la dieta del niño y de la madre en los que reciben leche materna. Para lograr la remisión de los síntomas y la tolerancia futura, la exclusión debe ser total. En los niños que reciben fórmula, esta deberá tener hidrolizado extenso de proteínas en las formas leves o moderadas, mientras que aquellas a base de aminoácidos se reservan para los casos más graves. El tiempo de tratamiento, la adquisición de tolerancia y el momento para la prueba de provocación oral van a variar según el cuadro clínico, el mecanismo inmunológico implicado y la edad del paciente. El objetivo de este consenso ha sido reflejar el conocimiento actualizado junto con la experiencia de neonatólogos, pediatras, especialistas en alergia, nutrición y gastroenterología.

The treatment of cow's milk protein allergy is based on the complete elimination of cow's milk protein from the diet. To achieve remission of symptoms and future tolerance, exclusion must be total. In formula fed infants the extensively hydrolysed formula is the most appropriate option in mild or moderate forms, while those based on amino acids are reserved for the most severe cases. The treatment time, the acquisition of tolerance and the moment for the oral provocation test will vary according to the clinical picture, the immunological mechanism involved and the age of the patient. The aim of this consensus has been to reflect the updated knowledge together with the experience of neonatologists, pediatricians, experts in allergy, nutrition and gastroenterology

Alergia a las proteínas de la leche de vaca: proceso diagnóstico. Consenso interdisciplinario de expertos / Cow's milk allergy: diagnostic process. Expert consensus

Las proteínas de la leche de vaca pueden causar alergia alimentaria. Los distintos mecanismos de acción involucrados y la variabilidad clínica según la etapa de la vida pediátrica en la que se manifieste ocasionan dificultades en su abordaje, con riesgo de sub- o sobrediagnóstico. En este proceso, intervienen profesionales de diversas áreas y es recomendable su interacción. Es por ello que el objetivo de este consenso ha sido reflejar el conocimiento actualizado desde la interdisciplina, generando recomendaciones para su correcto diagnóstico. Hemos trabajado con el método de Delphi para sumarle a la evidencia científica, la experiencia proveniente de neonatólogos, pediatras, especialistas en alergia, nutrición y gastroenterología. Pensamos que este enfoque interdisciplinario de trabajo va a resultar de utilidad práctica y promoverá una atención más integral de estos pacientes.

Cow's milk protein can cause food allergy. The different mechanisms of action involved, the clinical variability depending on the stage of pediatric life in which it manifests, leads to difficulties in its approach, with the risk of under- or over-diagnosis. Professionals from various areas intervene in this process and their interaction is recommended. That is why the objective of this consensus has been to reflect the updated knowledge in an interdisciplinary mode, generating recommendations for its correct diagnosis. We have worked with the Delphi method to add to the scientific evidence, the experience from neonatologists, pediatricians, experts in allergy, nutrition and gastroenterology. We think that this interdisciplinary approach will be of practical use and will promote more comprehensive care for these patients.

Association of pregnancy factors with cow's milk protein allergy in infants / 北京大学学报(医学版)

Objective:To preliminarily explore the association of pregnancy factors with cow's milk protein allergy in infants.Methods:This study was based on data from a subcohort of a study called ge-netic susceptibility to cow's milk allergy in Chinese children,including infants born in Peking University People's Hospital between March 1,2020,and December 31,2020.The infants were divided into a cow's milk protein allergy(CMPA)group and a control group according to whether they had developed cow's milk protein allergy at the age of 1 year.We retrospectively collected the clinical data of infants and their mothers before and during pregnancy,and analyzed the association of multiple factors during pregnancy with cow's milk protein allergy in infants.Results:A total of 278 infants were enrolled in this study,including 52 infants with CMPA and 226 infants without CMPA.Among them,there were 143 boys and 135 girls.The proportion of male infants in the CMPA group(69.2％)was higher than that in the control group(47.3％),and the difference was statistically significant(P=0.004).There were no significant differences in the distribution of birth weight,gestational age at birth,low-birth-weight in-fants,premature,umbilical cord entangle neck,and neonatal asphyxia between the CMPA group and the control group(P＞0.05).The proportion of mothers complicated with autoimmune diseases,anemia or antibiotics exposure during pregnancy in the CMPA group was higher than that in the control group,and there were statistical differences between the two groups(P＜0.05).There was no significant difference in the distribution of other pregnancy complications between the two groups(P＞0.05),such as eclamp-sia/preeclampsia,chronic hypertension/gestational hypertension,diabetes/gestational diabetes,thyroid diseases,and so on.There was no significant difference in the overall distribution of some blood routine indexes during pregnancy between the CMPA group and the control group(P＞0.05).Multivariate Lo-gistic regression analysis showed that male infant,mothers complicated with autoimmune diseases or ane-mia,antibiotic exposure during pregnancy were independent risk factors for cow's milk protein allergy.Conclusion:Male infant,mothers complicated with autoimmune diseases or anemia,antibiotic exposure during pregnancy were independent risk factors for cow's milk protein allergy.

Dynamic changes of platelet-related indicators in infants with cow′s milk protein allergy / 中国儿童保健杂志

【Objective】 To dynamically monitor and analyze the changes of platelets and related indicators in infants with cow′s milk protein allergy (CMPA) during clinical treatment, in order to provide clues for further diagnosis and treatment of CMPA. 【Methods】 From August to November in 2022, 59 children aged from 1 month to 3 years old with CMPA in the pediatric outpatient clinic were selected as the CMPA group, and 29 healthy children who took physical examination were selected as the control group. The differences in platelet related indicators from a routine blood test were compared between the two groups, and their diagnostic value for CMPA was analyzed by receiver operating characteristic (ROC) curves. 【Results】 The mean platelet count (PLT) and plateletcrit (PCT) at baseline in the CMPA group were (374.68±113.21)×109/L and 0.37±0.10, significantly higher than those in control group[(271.07±40.32)×109/L, 0.26±0.05] (t=6.27, 6.43, P<0.001). In the CMPA group, after treatment, the mean PLT level was (316.39±94.68)×109/L, and the mean PCT level was 0.31±0.10, indicating a statistically significant decrease in PLT and PCT levels after treatment compared to baseline (t=4.32,4.75,P<0.05). The diagnostic performance, indicated by the area under the curve (AUC), for PLT and PCT in diagnosing CMPA was 0.811 and 0.823, respectively. The cutoff values for PLT and PCT were determined to be 304.5×109/L and 0.305, respectively. 【Conclusion】 The PLT and PCT levels in children with CMPA are found to be higher than those in healthy controls, suggesting their potential diagnostic value in the diagnosis of CMPA.

Advances in butyrates and intestinal immune tolerance in children with cow′s milk protein allergy / 国际儿科学杂志

Cow′s milk protein allergy is common in infants, which is an abnormal immune reaction caused by the imbalance of intestinal immune tolerance system.Butyrates, the fermentation product of intestinal anaerobic bacteria, can be used as a histone deacetylase inhibitors and a ligand of G protein-coupled receptors to regulate intestinal innate immunity and adaptive immune function, thereby inducing intestinal immune tolerance in children with cow′s milk protein allergy, which has potential clinical therapeutic value for cow′s milk protein allergy.However, this theory is still only based on the exploration of mechanisms at the cellular and animal levels and has not been applied in the clinic.This article reviews the intestinal immune mechanism of cow′s milk protein allergy, the anabolism of butyrates and the important role of butyrates in intestinal immune tolerance of cow′s milk protein allergy, aiming to lay a theoretical foundation for further clinical application of butyrate-induced intestinal immune tolerance of cow′s milk protein allergy.

Guidelines for diagnosis and nutritional intervention of mild to moderate non-IgE mediated cow′s milk protein allergy in Chinese infants / 中华实用儿科临床杂志

Cow′s milk protein allergy (CMPA) is one of the most common presentations of food allergy seen in early childhood.It is an abnormal immune response caused by cow′s milk protein.CMPA can be clinically subdivided into either immediate-onset IgE mediated or delayed onset non-IgE mediated, or both.At present, concerns regarding the early and timely diagnosis of CMPA have been high-lighted over the years and there are many expert consensus on CMPA in China, but these consensus did not distinguish IgE mediated or non-IgE mediated CMPA.In view of the obvious clinical differences between the two type of CMPA and non-IgE mediated CMPA is more common in infancy, experts focus on pediatric gastroenterology, allergy/immunology, dermatology, nutrition and child healthcare convened by the Allergy Prevention and Control Professional Committee of Chinese Preventive Medicine Association present this guideline to help practitioners in primary care settings to early recognize and make suitable management of non-IgE mediated CMPA in China.The guideline incorporates the cutting-edge international guidance and the actual situation of Chinese children describing in detail the types, clinical features, diagnosis and nutritional intervention of non-IgE mediated CMPA.There are 42 recommendations in 7 categories in total referring to the common questions related to non-IgE mediated CMPA.

Growth of infants with gastrointestinal manifestations of cow's milk protein allergy / Crescimento de lactentes com manifestações gastrointestinais de alergia à proteína do leite de vaca

ABSTRACT Objective To assess linear growth and weight gain in infants with suspected cow's milk protein allergy with gastrointestinal manifestations, seen at a gastropediatrics clinic. Methods A retrospective cohort study conducted with demographic, clinical, anthropometric and dietary information on 84 infants first seen between 2015 and 2018 and followed-up for six months. Stature-for-age, weight-for-age, and body mass index-for-age in z-scores were evaluated according to the cut off points established by the World Health Organization in 2006. Accelerated growth or catch-up was considered a gain ?0.67 in the z-score of the referred indices, evaluated at 3 and 6 months. Results Median age at baseline was 4.0 months and 88.1% of the infants were already in diet exclusion. Regarding the anthropometric evaluation short stature frequency was 15.5% and the underweight frequency was 8.3% and 3.6% respectively based on the weight-for-age and body mass index-for-age indices. High recovery growth was observed during the follow-up period but was not considered catch up. In boys, the gains in weight-for-age and body mass index-for-age were significant (p=0.02 and p=0.01 respectively) and close to the threshold that characterizes the catch up, 0.58 and 0.59, respectively. In girls, significant gains in stature-for-age and weight-for-age (0.38 and 0.37 respectively, p=0.02 for both) were observed. Conclusion Infants with suspected cow's milk protein allergy with gastrointestinal manifestations should have early access to specialized nutritional counseling to avoid exposure to allergenic food and control allergy symptoms, thereby avoiding malnutrition and ensuring adequate nutritional recovery.

RESUMO Objetivo Avaliar o crescimento linear e o ganho de peso de lactentes com suspeita de alergia à proteína do leite de vaca, com manifestações gastrointestinais, atendidos em um ambulatório de gastropediatria. Métodos Estudo de coorte retrospectivo, com informações demográficas, clínicas, antropométricas e dietéticas de 84 lactentes que iniciaram atendimento entre 2015 e 2018 e foram acompanhados durante seis meses. Foram avaliados os índices estatura/idade, peso/idade e índice de massa corporal/idade em escore-z, segundo os pontos de corte da Organização Mundial de Saúde de 2006. Considerou-se crescimento acelerado (ou catch-up growth) um ganho ?0,67 escore-z nos referidos índices, avaliados em três e seis meses. Resultados No baseline, a mediana de idade foi 4,0 meses e 88,1% dos lactentes já estavam em dieta de exclusão. A frequência de baixa estatura foi de 15,5% e a de baixo peso foi de 8,3% e de 3,6% segundo os índices peso/idade e índice de massa corporal/idade, respectivamente. Houve elevado crescimento de recuperação durante o período de acompanhamento, mas que não configurou catch up. Nos meninos, ganhos no peso/idade e índice de massa corporal/idade foram significantes (p=0,02 e p=0,01) e próximos do limiar que caracteriza catch up: 0,58 e 0,59, respectivamente. Nas meninas, foram observados ganhos significantes na estatura/idade e peso/idade, de 0,38 e 0,37 (p=0,02 para ambos). Conclusão Demonstrou-se que lactentes com suspeita de alergia à proteína do leite de vaca, com manifestações gastrointestinais, deveriam ter acesso precoce ao aconselhamento nutricional para evitar exposição ao alimento alergênico, controlar sintomas e, assim, evitar a desnutrição ou garantir recuperação nutricional adequada.

Research progress of cow′s milk protein allergy and intestinal flora characteristics in premature infants / 中华实用儿科临床杂志

Cow′s milk protein allergy (CMPA) is the most common food allergy in infancy.Since the early symptoms of CMPA in premature infants lack specificity and are prone to misdiagnosis or missed diagnosis, which would induce inappropriate fasting and unreasonable application of antibiotics, more attention should be paid to CMPA in premature infants.It has been proved in accumulating studies that the establishment and improvement of intestinal flora is the basic factor for the maturation of the immune system and the induction of immune response balance after birth.There are differences in the type and amount of intestinal flora between food allergic infants and non-allergic infants.Compared with term infants, preterm infants have significantly lower diversity and abundance of intestinal flora, immature gastrointestinal tract and immune system development, and are at greater risk for allergies.The use of probiotics can enhance intestinal barrier function and improve immune tolerance.The clinical diagnosis and treatment of preterm CMPA, the characteristics of intestinal flora and the use of probiotics in preterm infants would be reviewed in this paper.

Effect of food avoidance therapy on gut microbiota in infants with cow′s milk protein allergy / 中国小儿急救医学

Objective:To investigate the effect of dietary avoidance therapy on gut microbiota in infants who were diagnosed as cow′s milk protein allergy by comparing the gut microbiota changes before and after the treatment.Methods:The infants with artificial feeding and clinical diagnosis of cow′s milk protein allergy were collected from the outpatient of Gastroenterology departement in our hospital.They were fed with amino acid formula instead of ordinary formula for 4 weeks.Among them, 23 cases of successful intervention were selected.The fecal samples before and after treatment were collected, and the fecal genomes were extracted respectively.The PCR products of specific segments of 16S rDNA were sequenced by high-throughput sequencing.The results were analyzed by bioinformatics, and the differences of flora composition before and after the intervention were compared to find the different species between groups.Results:No obvious difference was found between before and after treatment of gut microbiota diversity( P>0.05). The compose of gut microbiota of the cow′s milk protein allergy was changed after feeding with amino acid milk.At the level of phylum, proteobacteria decreased significantly after treatment.At the level of class, alphaproteobacteria and gammaproteobacteria decreased significantly.Enterobacteriaceae, enterobacteriaceae and streptococcus granulosus decreased significantly.At the family level, the number of peptostridium, peptostridium and clostridium decreased significantly compared with that before treatment.Lactobacillus eubacteriaceae and eubacterium, ruminococcaceae, limosum, pasteurella, pasteurellaceae, haemophilus parainfluenzae T3T1, infantis ATCC15697/JCM1222/DSM2008 and Pseudocatenulatum-DSM20438/JCM1200/LMG10505 were higher than that before treatment with statistically different( P<0.05). Conclusion:For children with cow′s milk protein allergy, the harmful bacteria in intestinal flora decreased and the beneficial bacteria increased after dietary avoidance treatment.

Research advances in animal models of cow's milk protein allergy / 国际儿科学杂志

Cow's milk protein allergy (CMPA) is the most common food allergy among infants and young children,which has an increasing incidence in recent years.Performing suitable animal experiments is a key to study CMPA,but currently there aren't proper models consistent with human physiological sensitization process.Ideal animal models can serve as critical tools to reveal the mechanisms of CMPA and develop preventive and therapeutic approaches.Animal species and strains,different types of the models,biological detection methods and evaluation are reviewed in this paper.It also summarizes characteristics of animal models,which will provide a reference for basic and applied researches of CMPA.