Milk allergy most burdensome in multi-food allergic children.

BACKGROUND: Food allergy is a substantial health burden, which disproportionately affects children. Among children with food allergy, as many as 70% have multiple food allergies. Whereas the overall burden of food allergy on quality of life has been described, little is known about the burden of individual allergens. We aimed to examine the perception of burden among families with multiple food-allergic children. METHODS: Parents of children with 1 + children with multiple food allergies including milk responded to online questions, including both open-ended and closed-ended questions on food allergy-related burdens of time, financial costs, social restrictions, and emotional demands. RESULTS: Overall, 64 children (69.8% boys) of whom (73.0%) most were aged 10 and younger were included. Most had been diagnosed with food allergy in infancy and by a (pediatric) allergist. Other common allergies included peanut (65.6%), tree nuts (57.8%), egg (76.6%), and sesame (31.3%). Quantitatively, milk allergy was reported as carrying the most burden, including most socially limiting (81.5%), requiring the most planning (75.9%), causing the most anxiety (68.5%), most challenging to find "safe" or allergy-friendly foods (72.2%), and costly (81.5%). Qualitatively, we identified five themes that captured burdens associated with costs, marketing of milk products to children, risk of cross-contamination, ubiquity of milk/dairy and public confusion with lactose intolerance, and an unwillingness of others to accommodate the allergy. CONCLUSION: Parents whose children have multiple food allergies, including milk, report milk as the allergy associated with the greatest time, financial, social, and emotional burdens.

Why do babies cry?

Persistent, inconsolable crying in young infants is common, distressing but usually benign. This selective review examines perceptions and perceived origins of this phenomenon in babies where serious pathology has been excluded. Adult brains have evolved to become hypersensitive to infant cries. Babies respond to parental stress by crying more, thus setting up a vicious cycle. Most treatments appear to work largely through a placebo effect. The imperative for healthcare professionals is to reduce parental anxiety by offering reassurance and support.

Gastrointestinal Symptoms of Food Challenge-proven Non-IgE Cow's Milk Allergy Are Dissipated by Early School Age.

OBJECTIVES: The aim of this study was to evaluate the current well-being and dietary restrictions in children 6 years after food challenge-confirmed diagnosis of non-IgE cow's milk protein allergy, compared to peers with gastrointestinal symptoms but negative food challenge. This study aimed to evaluate the diagnostic process retrospectively. METHODS: This is an Internet-based survey for mothers whose children underwent 6 years ago the double-blind, placebo-controlled food challenge for cow's milk (CM) because of gastrointestinal symptoms causing suspicion of non-IgE CM protein allergy. Concurrent dietary restrictions, overall well-being, medical history, and retrospective views on the food challenge were queried using a study-specific questionnaire, the Quality of life using PedsQL general score and parental stress with the Parenting Stress Index questionnaire. RESULT: Mothers of 42 children (23 girls), median age of 6.7 years (range 5.7-8.6), participated in the survey, the response rate was 70%. All children now consumed cow's milk protein. The only food restrictions reported were empirical lactose-free diets in 7 children (17%). One-third of the children in both groups were presently reported to have eating-related issues such as picky eating. Quality of life was good and present parenting stress was average in both groups. The majority of the mothers (87%) felt positive or neutral about the food challenge performed in infancy. CONCLUSIONS: The non-IgE CM allergy with gastrointestinal symptoms diagnosed in infancy was a transient condition with good outcome. At an early school age, nearly all children have a good quality of life and a regular diet. The use of the double-blind, placebo-controlled food challenge was well-endorsed.

Dietary interventions that reduce mTOR activity rescue autistic-like behavioral deficits in mice.

Enhanced mammalian target of rapamycin (mTOR) signaling in the brain has been implicated in the pathogenesis of autism spectrum disorder (ASD). Inhibition of the mTOR pathway improves behavior and neuropathology in mouse models of ASD containing mTOR-associated single gene mutations. The current study demonstrated that the amino acids histidine, lysine, threonine inhibited mTOR signaling and IgE-mediated mast cell activation, while the amino acids leucine, isoleucine, valine had no effect on mTOR signaling in BMMCs. Based on these results, we designed an mTOR-targeting amino acid diet (Active 1 diet) and assessed the effects of dietary interventions with the amino acid diet or a multi-nutrient supplementation diet (Active 2 diet) on autistic-like behavior and mTOR signaling in food allergic mice and in inbred BTBR T+Itpr3tf/J mice. Cow's milk allergic (CMA) or BTBR male mice were fed a Control, Active 1, or Active 2 diet for 7 consecutive weeks. CMA mice showed reduced social interaction and increased self-grooming behavior. Both diets reversed behavioral impairments and inhibited the mTOR activity in the prefrontal cortex and amygdala of CMA mice. In BTBR mice, only Active 1 diet reduced repetitive self-grooming behavior and attenuated the mTOR activity in the prefrontal and somatosensory cortices. The current results suggest that activated mTOR signaling pathway in the brain may be a convergent pathway in the pathogenesis of ASD bridging genetic background and environmental triggers (food allergy) and that mTOR over-activation could serve as a potential therapeutic target for the treatment of ASD.

Reintroduction failure is common among adolescents after double-blind placebo-controlled food challenges.

AIM: There has been a lack of research on adolescents who undergo double-blind placebo-controlled food challenges. The aim of this study was to investigate food allergic adolescents' experiences and consequences of double-blind placebo-controlled food challenges. METHODS: This qualitative, descriptive interview study included 17 adolescents aged 14-15 years with total elimination of cows' milk, hens' eggs or cod due to food allergies. The participants, who were initially identified from a large population-based cohort study, were interviewed 18 months after completing their challenges. RESULTS: The double-blind placebo-controlled food challenge proved to be a complex experience for the adolescents, involving fear of potential reactions and the hope that the food could be reintroduced. Experiences during the challenge were described in three themes: facing fears in a secure environment, being hesitant but curious about unknown tastes and waiting for unknown food reactions. Experiences after the challenge were described in two themes: gaining control and freedom and continuing old habits. A negative challenge was not consistently associated with the reintroduction of the challenged food. CONCLUSION: This study highlighted the importance of considering the adolescents' expectations and experiences of the challenge and the reintroduction process to ensure desirable changes in their dietary habits. Follow-ups should be performed regardless of the outcome of challenges.

Taste preference, food neophobia and nutritional intake in children consuming a cows' milk exclusion diet: a prospective study.

BACKGROUND: Taste exposure in infancy is known to predict food preferences later in childhood. This is particularly relevant in children with cows' milk allergy who consume a substitute formula and/or a cows' milk exclusion (CME) diet early in life. This prospective study aimed to show whether there is a long-term effect of consuming a substitute formula and CME diet on taste preferences and dietary intake. METHODS: Children were predominantly recruited from two large birth cohort studies in the UK. Two groups were recruited: an experimental group of children who had consumed a CME diet during infancy and a control group who had consumed an unrestricted diet during infancy. Parents completed a food neophobia questionnaire and an estimated prospective food diary. Children completed a taste preference test and their growth was assessed. RESULTS: One hundred and one children with a mean age of 11.5 years were recruited (28 CME and 73 controls). Children in the CME group had a significantly higher preference for bitter taste than those in the control group (P < 0.05). There were significant differences between the groups with respect to the intake of some micronutrients, including riboflavin, iodine, sodium and selenium. Food neophobia did not differ between groups. Some 28% of the CME group were overweight/obese compared to 15% of the control group; however, this difference was not statistically significant. CONCLUSIONS: Consuming a substitute formula and/or a CME diet in infancy has a long-term effect on the preference for bitter taste. Differences exist with respect to the intake of some micronutrients, but not macronutrients. There was a nonsignificant trend towards being overweight and obese in children in the CME group.

mTOR plays an important role in cow's milk allergy-associated behavioral and immunological deficits.

Autism spectrum disorder (ASD) is multifactorial, with both genetic as well as environmental factors working in concert to develop the autistic phenotype. Immunological disturbances in autistic individuals have been reported and a role for food allergy has been suggested in ASD. Single gene mutations in mammalian target of rapamycin (mTOR) signaling pathway are associated with the development of ASD and enhanced mTOR signaling plays a central role in directing immune responses towards allergy as well. Therefore, the mTOR pathway may be a pivotal link between the immune disturbances and behavioral deficits observed in ASD. In this study it was investigated whether the mTOR pathway plays a role in food allergy-induced behavioral and immunological deficits. Mice were orally sensitized and challenged with whey protein. Meanwhile, cow's milk allergic (CMA) mice received daily treatment of rapamycin. The validity of the CMA model was confirmed by showing increased allergic immune responses. CMA mice showed reduced social interaction and increased repetitive self-grooming behavior. Enhanced mTORC1 activity was found in the brain and ileum of CMA mice. Inhibition of mTORC1 activity by rapamycin improved the behavioral and immunological deficits of CMA mice. This effect was associated with increase of Treg associated transcription factors in the ileum of CMA mice. These findings indicate that mTOR activation may be central to both the intestinal, immunological, and psychiatric ASD-like symptoms seen in CMA mice. It remains to be investigated whether mTOR can be seen as a therapeutic target in cow's milk allergic children suffering from ASD-like symptoms.

Monitoring the impact of cow's milk allergy on children and their families with the FLIP questionnaire--a six-month follow-up study.

BACKGROUND: Many children with cow's milk allergy (CMA) develop tolerance, but, challenges in daily life may remain. Using the Food hypersensitivity famiLy ImPact questionnaire (FLIP), we sought to monitor changes in the impact of CMA over time. METHODS: Families of children with CMA, who participated in the validation of the FLIP, were re-approached 6 months later for follow-up. Change in reported difficulties was assessed by paired sample t-test and mixed models, stratifying by outgrown vs. persistent CMA. RESULTS: Impact on families with children who had outgrown CMA (n = 20) decreased in the FLIP's total score (p = 0.0001) and in two subscales; Health and Emotions (p = 0.0001) and Everyday Life (p = 0.0001). In contrast, no significant improvements were registered in nutritional concerns. Impact on the group with persistent CMA (n = 57) was unchanged at follow-up except for more impact on Everyday Life (p = 0.001). In the final analysis comparing longitudinal changes in the groups, the strongest differences were observed for the subscales Health & Emotions and Everyday Life; for the Nutrition subscale, the between-group changes also differed, but to lesser extent. CONCLUSIONS: We have documented the varying impact of CMA on parents and children over time. Families who were still affected continued to experience impact in daily life. Despite development of tolerance, families who were no longer affected revealed continuing nutritional concerns. Follow-ups should be offered even after outgrown CMA to encourage progression to unrestricted diet, to prevent eating disorders and to promote healthy growth.

How mothers perceive infants with unspecific gastrointestinal symptoms suggestive of cow's milk allergy?

AIM: To determine whether specific infant behavioural characteristics are present in children suspected of cow's milk allergy because of gastrointestinal symptoms. METHODS: We prospectively recruited 57 children (median age 8.7 months) with a suspicion of gastrointestinally manifested cow's milk protein allergy (GI-CMPA). None had detectable cow's milk-specific IgE. Mothers were asked to complete the Parenting Stress Index (PSI) Child Domain, and those with children below 18 months of age (n = 49) also the Infant Temperament Questionnaire (ITQ). GI-CMPA was diagnosed with the double-blind, placebo-controlled food challenge. Control group (n = 22) consisted of patients (age range 4-26 months), attending the Pediatric Allergy Unit, who did not have diagnosed or suspected food allergies. RESULTS: The scores were significantly higher for the PSI (n = 48) Child Domain (p < 0.0001) and for the ITQ (n = 44) subscale Difficultness (p = 0.0045) compared with the control patients without suspected/diagnosed food allergy. The difference between the challenge positive (n = 18) and negative (n = 39) patients remained statistically insignificant. After 6 months, in both groups, the scores (PSI Child Domain p = 0.0004, ITQ Difficultness p = 0.0393) were lower, but the ITQ Difficultness score still remained higher than in the controls (p = 0.0453). CONCLUSION: The mothers often perceive infants with unspecific symptoms suggestive of GI-CMPA as demanding and temperamentally difficult.

How mothers interact with children with suspected cow's milk allergy symptoms.

AIM: To characterize mother-child interaction in children with suspected gastrointestinally manifested cow's milk allergy (GI-CMA) and to explore factors associated with the parentally perceived symptoms. METHODS: We invited a randomly selected group of children with suspected GI-CMA and their mothers to take part in a video recording of them playing together. The mother-child interaction was rated using the Emotional Availability Scales (EAS, 4th edition) and compared with national normative data. RESULTS: Video recordings were conducted with 24 patients (15 girls and nine boys) with a median age of 10.1 months (range 2.1-20.5 months) undergoing a double-blind, placebo-controlled food challenge for cow's milk allergy. The EAS profile in the challenge negative group (17/24) was significantly different from the normative data. The scores for maternal sensitivity (p = 0.0049) and nonintrusiveness (p = 0.0192), together with child responsiveness (p = 0.0053) and involvement of mother (p = 0.0085), were all significantly lower when compared to the normative data. The dimensions of maternal nonhostility and structuring, as well as the scores of the challenge positive group, did not differ from the normative data. CONCLUSION: Dysfunctional mother-child emotional interaction was frequent in young children with suspected GI-CMA ruled out by the cow's milk challenge. Appropriate psychological support should be considered.

Impact of oral immunotherapy on quality of life in children with cow milk allergy: a pilot study.

Quality of life is negatively affected in children with food allergy. Oral immunotherapy is an approach to food allergy that leads to patient desensitization by administering gradually increasing amounts of a given food allergen. The aim of this pilot study is to evaluate how oral immunotherapy affects quality of life in children allergic to cow milk proteins. Thirty children (aged 3-12 years) with cow milk allergy were recruited. Their parents were provided with a validated disease specific quality of life questionnaire (the food allergy quality of life questionnaire -- parent form, FAQLQ-PF) before and again 2 months after completing an oral immunotherapy protocol with cow milk. A significant improvement in all the investigated domains -- emotional impact, food anxiety and social and dietary limitations -- was found. The separate analysis of the different age groups demonstrated that the emotional impact and the food-related anxiety improved in children older than 4, while the social domains improved in each age group. In this pilot experience, oral immunotherapy significantly improves quality of life in children with cow milk allergy. The improvement seems particularly evident in children over 4 years old, who are most likely to benefit from the oral immunotherapy approach. Further placebo-controlled studies are needed to confirm these preliminary results.

Self-reported milk intolerance in irritable bowel syndrome: what should we believe?

BACKGROUND & AIMS: The real importance of lactose malabsorption in irritable bowel syndrome (IBS) is still controversial. The aim is to define the relationship between patient perception of milk tolerance/intolerance, lactose malabsorption and abdominal symptoms in IBS. METHODS: A hydrogen breath test (HBT) after an oral load of lactose was carried out in 475 consecutive IBS patients, diagnosed according to the Rome criteria. Data were analyzed in 201 age- and sex-matched pairs of IBS patients, classified according to self-reported milk tolerance/intolerance. Hydrogen peak and excretion, predominant presenting symptom and the occurrence of symptoms during the test, were evaluated. RESULTS: The prevalence of positive HBT and the occurrence of symptoms during the test was similar in milk "tolerant" (68.6%, 40.7% respectively) and "intolerant" patients (75.6%, 42.7% respectively), as well as peak (76.4 vs 75.2 ppm) and amount of H2 excreted (57.8 vs. 53.2 ppm/h). The positive predictive value for self-reported milk intolerance was 0.75, and the negative predictive value in regular milk users was 0.31, reflecting the prevalence of lactose malabsorption in the general population more than the awareness of milk tolerance. CONCLUSIONS: In IBS patients, self-reported milk intolerance does not help in identifying lactose malabsorbers. The opposite does not rule out the occurrence of symptoms after a lactose load. Lactose is, indeed, responsible for symptoms in some IBS patients, however, these patients can only be identified by the occurrence of symptoms during the test, and not on the individual perception of milk intolerance.

Restricted diets in children with reactions to milk and egg perceived by their parents.

The aim of this study was to investigate the degree to which parents alter the diets of their children on the basis of perceived reactions. From a population-based sample of 2979 2-year old children with reactions to egg or milk perceived by their parents, one third had strict limitations on the intakes of these foods, representing 2.5% of the children in the cohort. In approximately 1 of 6 families the strict diets were initiated without consulting a doctor, and in a substantial proportion the restrictions were unwarranted. High maternal education level and irritability attributed to food were among the risk factors for unwarranted diets. On the other hand, many children, in whom an adverse reaction was verified, lacked appropriate diet restrictions. We conclude that the handling of adverse reactions to food frequently occurs outside the medical care system at the cost of correct diagnosis and appropriate diets.