Consumption of cow's milk formula in the nursery and the development of milk allergy.

BACKGROUND: The effect of the amount of transient cow's milk formula (CMF) consumed during the first days of life on IgE-cow's milk allergy (IgE-CMA) is unknown. METHODS: A cohort of 58 patients with IgE-CMA was identified from a large scale population-based study of 13,019 infants followed from birth. A group of 116 infants matched for sex and breastfeeding only duration (beyond the nursery period), and another random group of 259 healthy infants were used as controls. Parents were interviewed and the infants' medical records were searched to assess CMF consumption in the nursery. RESULTS: While 96% of the mothers of the 174 infants (58 with Cow's milk allergy and 116 controls) reported on exclusive breastfeeding during the stay in the nursery, CMF consumption was documented in 96 (55%) of the infants. Of those, most (57; 59%) received one to three feedings, 20 (21%) received four to nine feedings, and 19 (20%) received ≥10 feedings. Fewer formula feeds (1-3) were significantly more common in the allergic group than ≥4 feeds (p = 0.0003) and no feeds at all (p = 0.02) compared to controls (n = 116). Of those exclusively breastfed in the nursery, 13/23 allergic infants (57%) introduced CMF at age 105-194 days (the period with highest-risk for IgE-CMA) compared to 33/98 (34%) from the random control group (n = 259) (p = 0.04). CONCLUSIONS: Most infants end up receiving few CMF feeds in the nursery. Transient CMF in the nursery is associated with increased risk of IgE-CMA.

Sesame eliciting and safe doses in a large sesame allergic population.

BACKGROUND: Sesame is a significant food allergen causing severe and even fatal reactions. Given its increasing prevalence in western diet, sesame is listed as an allergenic food requiring labeling in the United States and EU. However, data on the population reaction doses to sesame are limited. METHODS: All sesame oral food challenges (OFCs), performed either for diagnosis or for threshold identification before the beginning of sesame oral immunotherapy (OIT) between November 2011 and July 2021 in Shamir medical center were analyzed for reaction threshold distribution. Safe-dose challenges with 90-120 min intervals were also analyzed. RESULTS: Two hundred and fifty patients underwent 338 positive OFCs, and additional 158 safe-dose OFCs were performed. The discrete and cumulative protein amounts estimated to elicit an objective reaction in 1% (ED01) of the entire cohort (n = 250) were 0.8 mg (range 0.3-6.3) and 0.7 mg (range 0.1-7.1), respectively, and those for 5% of the population (ED05) were 3.4 mg (range 1.2-20.6) and 4.5 mg (range 1.2-28.8), respectively. Safe-dose OFCs showed similar values of ED01 (0.8, 0.4-7.5 mg) and ED05 (3.4, 1.2-22.9 mg). While doses of ≤1 mg sesame protein elicited oral pruritus in 11.6% of the patients, no objective reaction was documented to this amount in any of the challenges, including safe-dose OFCs. CONCLUSIONS: This study provides data on sesame reaction threshold distribution in the largest population of allergic patients studied, with no right or left censored data, and with validation using a safe-dose OFC. It further supports the current methods for ED determination as appropriate for establishing safety precautions for the food industry.

Severe Anaphylactic Reactions to Home Doses of Oral Immunotherapy for Food Allergy.

BACKGROUND: Severe anaphylactic reactions to home doses may occur during food allergy oral immunotherapy (OIT). OBJECTIVE: To study the rate and risk factors for such reactions. METHODS: We studied all patients aged greater than 3.5 years who completed OIT in a single center between April 2010 and January 2020. All home epinephrine-treated reactions (HETRs) were identified. High-grade HETRs (HG-HETRs) were defined as HETRs involving respiratory (SpO2 of 94% or less), cardiovascular (low blood pressure), or central nervous system impairment (loss of consciousness). We investigated the rate and risk factors for HG-HETRs. RESULTS: A total of 1,637 OIT treatments were studied: milk (880), peanut (346), tree nuts (221), sesame (115), and egg (75). Of 390 identified HETRs, 30 HG-HETRs occurred during 27 treatments (1.65% of all treatments). Nearly all (26 of 30) were during milk OIT in patients with house dust mite (HDM) sensitization and asthma (26 of 30 each). Of the 30 patients with HG-HETRs, 21 recovered with one or two epinephrine treatments, but nine (0.55% of all treatments) did not respond to a second dose of epinephrine and were deemed to have refractory anaphylaxis. Three patients required intensive care unit admission and three received epinephrine drip, but none required ventilatory support. Risk factors for HG-HETRs included milk OIT (P = .031), asthma (P = .02) and HDM sensitization (P = .02). No specific triggers for HG-HETR were identified. Of patients with HG-HETRs, 25.9% were fully desensitized, including the four non-milk treated patients; 22.2% were partially desensitized; and 51.9% failed. CONCLUSIONS: High-grade HETRs are uncommon, particularly refractory anaphylactic reactions to home OIT doses. Although milk OIT, asthma, and HDM sensitization are the main risk factors for such reactions, identification of patients who are at risk is challenging.

Efficacy and safety of food allergy oral immunotherapy in adults.

BACKGROUND: Oral immunotherapy (OIT) is an emerging method for treating food allergy in children. However, data regarding adults undergoing this process are lacking. METHODS: We retrospectively analyzed the medical records of patients with food allergy aged ≥17 years who completed OIT treatment between April 2010 and December 2020 at Shamir Medical Center. Data were compared with that of children aged 4 to <11 years and adolescents aged ≥11 to 17 treated during the same time period. RESULTS: A total of 96 adults at a median age of 22.3 years who underwent OIT for milk (n = 53), peanut (n = 18), sesame (n = 7), egg (n = 5), and tree nuts (n = 13) were analyzed and compared with 1299 children and 309 adolescents. Adults experienced more adverse reactions requiring injectable epinephrine, both during in-clinic up-dosing (49% vs. 15.9% and 26.5% for children and adolescents, respectively, p < 0.0001) and during home treatment (22.9% vs. 12.4%, p = 0.007 for children, and 17.5%, p = 0.23 for adolescents). Most adults (61.5%) were fully desensitized, but the rates of full desensitization were significantly lower than children (73.4%, p = 0.013). Significantly more adults (28.3%) undergoing milk OIT failed treatment than children (14.3%, p = 0.015) and adolescents (14.1%, p = 0.022), while failure rates in adults undergoing OIT for other foods were low (9.3%) and comparable with children and adolescents. CONCLUSIONS: OIT is successful in desensitizing most adults with IgE-mediated food allergy. Adults undergoing milk OIT are at increased risk for severe reactions and for OIT failure while failure rates in adults undergoing OIT for other foods are low.

Factors associated with home epinephrine-treated reactions during peanut and tree-nut oral immunotherapy.

BACKGROUND: Home reactions requiring epinephrine administration, a marker of their severity, restrict the widespread use of oral immunotherapy (OIT), but their risk factors are largely not known. OBJECTIVE: To identify risk factors for such reactions during OIT to most allergenic foods. METHODS: All patients who began OIT for peanut, tree nuts, sesame, or egg allergy at the Shamir Medical Center between April 2010 and January 2020 were enrolled. The patients were instructed to use their epinephrine autoinjectors during reactions consisting of severe abdominal pain, significant shortness of breath, or lethargy, or whenever in uncertainty of reaction severity. Patients with and without home epinephrine-treated reactions (HETRs) were compared. RESULTS: A total of 757 OIT treatments for peanut (n = 346), tree nuts (n = 221; walnut n = 147, cashew n = 57, hazelnut n = 16, almond n = 1), sesame (n = 115), and egg (n = 75) allergies were administered to 644 patients. Eighty-three (10.9%) patients experienced HETRs. The highest rate of HETRs was experienced during walnut (20.4%) or hazelnut (25%) OIT, followed by peanut (9.8%), sesame (6.1%), egg (6.7%), and cashew (5.3%) OIT. Risk factors for HETRs included a reaction treated in an emergency department (ER) (P = .005) before starting OIT and a reaction treated with epinephrine during in-clinic induction (P < .001). Significantly fewer patients with (73.6%) than without (88.3%) HETRs achieved full desensitization (P = .001), but only a few patients with HETRs (8.4%) failed treatment. CONCLUSION: Previous reaction severity is the main predictor for HETRs during OIT. These reactions are more frequent during walnut and hazelnut OIT than during OIT for other foods studied. Most patients experiencing HETRs achieved desensitization.

Informing Risk Management for Patients With Cow's Milk Allergy Based on Threshold Dose Distributions Using Low-Dose Food Challenges.

BACKGROUND: The safe consumption of foods depends on their allergen content in relation to patients' lowest observed adverse effect level (LOAEL) and no observed adverse effect level (NOAEL), as well as other factors. In the case of milk, data on LOAEL and NOAEL are limited and conflicting. OBJECTIVE: To determine the threshold dose distribution and the lowest individual eliciting dose (ED) for milk in a large group of milk-allergic patients METHODS: Individuals with confirmed cow's milk allergy who underwent a diagnostic or pre-oral immunotherapy open milk oral food challenge at the Institute of Allergy, Immunology, and Pediatric Pulmonology at Shamir Medical Center between 2010 and 2015 were included. A subgroup of patients with severe milk allergy underwent a modified challenge with a 90- to 120-minute interval after a starting dose of 0.3 mg cow's milk protein. RESULTS: A total of 866 participants (193 with diagnostic challenges and 673 with pre-oral immunotherapy challenges) were included in the study. The discrete ED01 and ED05, or values derived in which 1% or 5% of the respective allergic population would be predicted to experience an allergic reaction, were 1.1 to 1.9 and 4.7 to 5.6 mg milk protein, respectively, and values for cumulative doses for ED01 and ED05 were 0.9 to 1.8 and 5.2 to 6.2 mg milk protein, respectively. No patients, including the most severely milk-allergic individuals who underwent the modified challenge, reacted to the first 0.3 mg protein dose. CONCLUSION: This report provides valuable information about milk NOAELs, LOAELs, and EDs that might assist regulators in decisions about food labeling in general, and milk in particular.

Detection and management of milk allergy: Delphi consensus study.

BACKGROUND: There is significant overdiagnosis of milk allergy in young children in some countries, leading to unnecessary use of specialized formula. This guidance, developed by experts without commercial ties to the formula industry, aims to reduce milk allergy overdiagnosis and support carers of children with suspected milk allergy. METHODS: Delphi study involving two rounds of anonymous consensus building and an open meeting between January and July 2021. Seventeen experts in general practice, nutrition, midwifery, health visiting, lactation support and relevant areas of paediatrics participated, located in Europe, North America, Middle East, Africa, Australia and Asia. Five authors of previous milk allergy guidelines and seven parents provided feedback. FINDINGS: Participants agreed on 38 essential recommendations through consensus. Recommendations highlighted the importance of reproducibility and specificity for diagnosing milk allergy in children with acute or delayed symptoms temporally related to milk protein ingestion; and distinguished between children directly consuming milk protein and exclusively breastfed infants. Consensus was reached that maternal dietary restriction is not usually necessary to manage milk allergy, and that for exclusively breastfed infants with chronic symptoms, milk allergy diagnosis should only be considered in specific, rare circumstances. Consensus was reached that milk allergy diagnosis does not need to be considered for stool changes, aversive feeding or occasional spots of blood in stool, if there is no temporal relationship with milk protein ingestion. When compared with previous guidelines, these consensus recommendations resulted in more restrictive criteria for detecting milk allergy and a more limited role for maternal dietary exclusions and specialized formula. INTERPRETATION: These new milk allergy recommendations from non-conflicted, multidisciplinary experts advise narrower criteria, more prominent support for breastfeeding and less use of specialized formula, compared with current guidelines.

Triggers for Home Epinephrine-Treated Reactions During Oral Immunotherapy for Food Allergy.

BACKGROUND: Home reactions requiring epinephrine treatment represent a significant obstacle to oral immunotherapy (OIT) and impair treatment outcome. OBJECTIVE: To identify potential triggers for such reactions for improvement of patient safety. METHODS: All patients aged older than 3.7 years who began an open-label OIT treatment program to milk, peanut, egg, sesame, or tree nuts in the Institute of Allergy, Immunology, and Pediatric Pulmonology at Shamir Medical Center between April 2010 and March 2018 were enrolled. Information on home epinephrine-treated reactions (HETRs) during the up-dosing phase of OIT was collected from the documentation in patients' files and the reports were transmitted by email and via a web reporting system. RESULTS: A total 1,270 OIT treatments were included (milk 780; peanut 256; egg 63; sesame 72; and tree nuts 99). Home epinephrine was administered in 200 treatments (15.7%) and in 70 of them a second epinephrine-treated reaction occurred. The leading identified triggers for HETRs were physical exercise temporally associated with administration of home dose (20%), and dose consumption during infectious disease (16.7%), or when fatigued (13.8%). The rate of first HETRs was highest (10.1%) to doses of 500 mg protein or less and particularly to 300 mg or less. The occurrence of first HETRs was highest (35.5%) during the first and decreased to 13.8% by the last of the 4-week home-treatment phase. Second HETRs occurred in a similar rate throughout these 4 weeks. The incidence of HETRs was highest during pollen season and vacation months. CONCLUSIONS: The identification of factors, some protocol-dependent, that trigger HETRs should assist in improving OIT safety.

Characteristics and associated morbidities of young adults with misconceived food allergy: A cross-sectional study.

BACKGROUND: Many patients with self-reported food allergy are not allergic but suffer from similar burdens. We aimed to characterize young adults with misconceived food allergy. METHODS: A cross-sectional study of individuals (n = 12,592) aged 17-18 years, recruited to the Israel Defense Forces (IDF) at a single urban-area recruitment center over a six month-period. All participants underwent a comprehensive medical and psychological evaluation. Cognitive tests were performed and a Combined Intellectual-Education score assigned. Participants who reported food elimination due to allergy were skin-tested and underwent oral food challenges, when indicated. The characteristics, psychological evaluation and cognitive tests of individuals with no reported food allergy (n = 12,444), misconceived food allergy (n = 64) and true food allergy (n = 84) were compared. FINDINGS: The prevalence of atopic co-morbidities was higher in recruits reporting compared to those not reporting food allergy while the rate of other co-morbidities was comparable. Anxiety disorder was diagnosed significantly more in individuals who reported food allergy (4·1%) compared to those who did not (1·7%) (p = 0·04). Further analysis revealed that this diagnosis was concentrated in individuals with misconceived (8/64, 12·5%) compared to true food allergy (2/84, 2·4%), (p = 0·02). Patients with misconceived food allergy were mostly of female sex, had lower Combined Intellectual-Education scores compared to patients with true (p = 0·001) and no reported food allergy (p = 0·01), and required the longest mean evaluation time (147·6 ± 109·4 days). INTERPRETATION: Patients with misconceived food allergy have higher rates of anxiety disorder and are often from a lower educational level and of female sex. Medical and educational attention is required to improve care of this specific population. FUNDING: The research reported in this publication was supported by the Israel Defense Forces (IDF) Medical Corps and Directorate of Defense Research & Development, Israeli Ministry of Defense (IMOD DDR&D).

Patient Characteristics and Risk Factors for Home Epinephrine-Treated Reactions During Oral Immunotherapy for Food Allergy.

BACKGROUND: Oral immunotherapy (OIT) is effective in desensitizing food-allergic patients but adverse events limit its applicability. OBJECTIVE: To identify risk factors for home epinephrine-treated reactions during the build-up phase of OIT. METHODS: A retrospective cohort study of patients older than 3.7 years undergoing OIT for food allergy at Shamir Medical Center between April 2010 and March 2019. All patients with a final disposition of full desensitization, partial desensitization, or failure were analyzed. Risk factors and outcome of home epinephrine-treated reactions were examined. RESULTS: A total of 1037 patients (mean age, 8.4 years) who underwent 1100 OIT treatments (milk, n = 710; peanut, n = 213; egg, n = 50; sesame, n = 57; and tree nuts, n = 70) reached a final disposition and were analyzed. Full desensitization was achieved in 763 (69.4%) treatments, partial desensitization in 219 (19.9%), and 118 (10.7%) failed. Epinephrine was administered to 121 patients (11.7%) during 10.8% of treatments. Milk OIT was a significant risk factor both for epinephrine-treated reactions (odds ratio, 2.15; 95% CI, 1.25-3.68) and for low rate of full desensitization following such reactions compared with nonmilk OIT (18.2% vs 73.9%, respectively; P < .0001). Risk factors during milk OIT included asthma, pre-OIT reaction severity, lower tolerated dose, and epinephrine-treated reactions during clinic updosing, whereas risk factors during nonmilk OIT were male sex and lower tolerated dose. CONCLUSIONS: Milk OIT poses a significant risk for home epinephrine-treated reactions during OIT and for poor outcome following such reactions. Together with the additional risk factors described for both milk and nonmilk OIT, this information may assist in patient selection for treatment.

Risk Factors and Treatment Outcomes for Oral Immunotherapy-Induced Gastrointestinal Symptoms and Eosinophilic Responses (OITIGER).

BACKGROUND: We recently described that oral immunotherapy (OIT)-induced gastrointestinal symptoms were associated with peripheral eosinophilic responses (termed OITIGER). OBJECTIVE: To identify treatment outcomes after dose modification and risk factors for developing OITIGER. METHODS: Treatment modifications in patients with OITIGER (n = 65) including cumulative dose reductions or treatment suspension were individualized and based on the severity of symptoms and an associated absolute eosinophil count (AEC, eosinophils/µL) of more than 900. Multivariate analysis for risk factors associated with OITIGER was performed in milk-OIT subjects. RESULTS: Treatment modifications reduced the cumulative daily dosage load by a median of 50% (interquartile range, 50%-67%) in 43 of 65 (66.1%) patients, deferred dose increases in 2 of 65 (3.1%) patients, or temporarily suspended treatment in 18 of 65 (27.7%) patients. Two patients (3.1%) had no treatment intervention. Symptoms and eosinophilia abated on dosage modification, allowing for resumption of dose increases (n = 34) or reinitiation of treatment (n = 9) after a median of 29 (interquartile range, 20-56) and 19 (interquartile range, 17-44) days, respectively. OITIGER reoccurred during treatment in 10 of 54 (18.5%) patients, which resolved after further dose modification. In long-term follow-up (>3-26 months), 31 of 32 patients were asymptomatic with stable AECs. Patients with OITIGER had a higher OIT failure rate (P = .004) and were less likely to reach full desensitization (P < .001), as compared with asymptomatic patients (n = 684). Multivariate analysis identified several risk factors for OITIGER: starting dose more than 120 mg (P < .001; odds ratio, 7.14), second-month dose more than 4-fold over the starting dose (P = .037; odds ratio, 2.18), and baseline AEC more than 600/µL (P = .002; odds ratio, 3.2). CONCLUSIONS: OITIGER is transient or reversible in most subjects, and its occurrence is related to OIT starting dose, its rate of increase, and baseline AECs.

The Prevalence of Food Allergy in Young Israeli Adults.

BACKGROUND: Information regarding the prevalence of food allergy (FA) among adults is limited due to their inaccessibility for thorough epidemiological evaluations. OBJECTIVE: To evaluate the prevalence of FA among Israeli young adults. METHODS: All recruits (n = 12,592, ages 17-18 years) signing up over 6 months at a single recruitment center of the Israeli army were evaluated for FA. The evaluation included a frontal interview by physicians who used a focused screening set of questions, medical documentation collection, tests of IgE reactivity, and oral food challenges. The latter were performed at an allergy care institute in ambiguous cases. A prediction model for the identification of individuals with true allergy among recruits eliminating foods due to suspected FA was developed using multivariable logistic regression. RESULTS: Foods elimination due to suspected FA was reported by 148 recruits (1.2%). After diagnostic testing, FA was confirmed in 0.67% (84 of 12,592). The prevalence of food elimination versus diagnosed allergy was 0.2%/0.16% milk, 0.2%/0.14% peanuts, 0.13%/0.09% fish, 0.1%/0.09% sesame, 0.04%/0.015% egg, and 0.36%/0.28% tree nuts, respectively. On multivariable logistic regression analysis, male gender (adjusted odds ratio [OR] = 3.2, 95% confidence interval [CI]: 1.4-7.7), report of a common food allergen (OR = 3.6, 95% CI: 1.4-9.3), previous allergist evaluation for FA (OR = 7.8, 95% CI: 3-20.2), and FA reactions within the past 2 years (OR = 2.8, 95% CI: 1.2-6.7) were significantly identified as independent predictors of true FA. CONCLUSIONS: The prevalence of FA among Israeli young adults is lower than reported for other western countries. Reliance on food elimination alone does not accurately rule in FA. The use of the identified predictors for FA can facilitate large-scale epidemiological studies in adults.

Efficacy and Safety of Sesame Oral Immunotherapy-A Real-World, Single-Center Study.

BACKGROUND: The presence of sesame in Western diet is increasing, making its avoidance by sesame-allergic patients more challenging. OBJECTIVE: To report the efficacy and safety of sesame oral immunotherapy (OIT). METHODS: Sixty patients aged 4 years or older, diagnosed as sesame-allergic on the basis of a positive oral food challenge, were consecutively enrolled into OIT between November 2014 and November 2017. Fifteen patients with sesame allergy, based on a positive oral food challenge or a recent immediate reaction, and a positive skin prick test result or specific IgE, continued sesame elimination and served as observational controls. Immunologic parameters were measured in a subset (OIT, n = 16; controls, n = 11) at the start and end of the study. Fully desensitized patients continued daily consumption of 1200 mg sesame protein and challenged with 4000 mg after more than 6 months. RESULTS: Fifty-three OIT-treated patients (88.4%) were fully desensitized to sesame, compared with 0% of controls. Four additional patients (total 57 of 60 = 95%) were desensitized to more than 1000 mg protein. Reactions occurred in 4.7% of hospital doses and 1.9% of home doses. Epinephrine-treated reactions occurred in 16.7% of patients for hospital and 8.3% for home doses. Significant decreases in rSes i 1 IgE (P = .007) and basophil reactivity (P = .001) and increases in sesame and rSes i 1 IgG4 (P = .001) occurred in OIT-treated patients but not in controls. Forty-seven patients desensitized to 4000 mg were evaluated more than 6 months after reaching maintenance. Only mild reactions were reported during maintenance, and all passed the 4000-mg challenge. CONCLUSIONS: Sesame-OIT is an effective alternative to sesame avoidance in allergic patients. The potential for adverse events necessitates its performance in specialized centers.

Reduced Final Height and Inadequate Nutritional Intake in Cow's Milk-Allergic Young Adults.

BACKGROUND: Growth impairment was previously described in milk-allergic children but was not examined in adults on reaching final height. OBJECTIVES: To investigate the dietary intake and final stature of young adults with IgE-mediated cow's milk allergy (IgE-CMA) as compared with nonallergic controls. METHODS: Eighty-seven patients with IgE-CMA, median age 19.5 years (interquartile range [IQR], 17.3-22.7), and 36 control participants without food allergies, median age 22.7 years (IQR, 18.9-26.1), were studied. Anthropometric and nutritional data were collected. Age and gender z-scores were determined according to the Centers for Disease Control and Prevention growth charts. Nutrient intake assessment was based on dietary records. Individuals with conditions or treatments affecting bone metabolism or growth, other than asthma, were excluded. RESULTS: Mean values of height z-scores were significantly reduced in CMA subjects compared with controls (-0.64 ± 0.9 vs -0.04 ± 0.7, P = .001). In contrast, no differences were found between the 2 groups in weight and body mass index z-scores. Patients with CMA had significantly lower intake of protein, and several essential vitamins (A, B12, and riboflavin) and minerals (calcium, potassium, phosphorus, magnesium, and zinc) compared with controls (P < .05), but the intakes of calories, carbohydrate, and fat were not significantly different between the 2 groups. Differences between actual and expected (based on midparental height) height z-scores were comparable in CMA subjects with or without asthma and between those with and without additional food allergies. CONCLUSIONS: Young adults who have CMA from infancy are at risk of not reaching their growth potential. Growth and nutritional monitoring and appropriate dietary intervention are of particular importance in these at-risk individuals.

Consumption of soy-based infant formula is not associated with early onset of puberty.

PURPOSE: The use of soy products is common in young children with cow milk allergy (CMA). The aim was to examine prospectively the association between infantile consumption of soy-based formula, growth parameters and early pubertal signs, in comparison to cow milk-based formula. METHODS: A nested case-control study was conducted, selected from a cohort of infants prospectively followed from birth until the age of 3 years for eating habits and the development of IgE-mediated CMA. Infants who consumed only soy-based formula were included in the soy group. The control group was randomly selected from those without IgE-CMA and not receiving soy formula. Study participants were reevaluated between ages 7.8 and 10.5 years by an interview, nutritional intake by 3 days diaries, and height, weight, and pubertal signs by physical examination. RESULTS: The soy-fed group included 29 participants (17 males), median age 8.92 years IQR (8.21, 9.42). The control group included 60 participants (27 males), median age 8.99 years IQR (8.35, 9.42). The groups had comparable height and BMI z scores (- 0.17 ± 1.08 versus - 0.16 ± 1.01, p = 0.96, and 0.67 ± 1.01 versus 0.53 ± 1.02, p = 0.56, for soy and control groups, respectively). Four (three males and one female) from the soy-group (13.8%) and eight females from the control-group (13.3%) had early pubertal signs (p = 0.95). No association was detected between puberty and infantile nutrition, after controlling for BMI and family data. No association with puberty or differences between groups were found in current daily consumption of soy, micronutrients, energy, carbohydrates, fat, and protein. CONCLUSIONS: This is the first prospective, physical examination-based study, demonstrating no association between infantile soy-based formula consumption and growth and puberty parameters.

Risk factors for reduced bone mineral density measurements in milk-allergic patients.

BACKGROUND: Earlier studies noted that young adults with IgE-mediated cow's milk allergy (IgE-CMA) have significantly lower bone mineral density (BMD) than age- and gender-matched controls. We sought to identify additional risk factors contributing to the low BMD in IgE-CMA patients. METHODS: Postpubertal (defined by Tanner stage V) IgE-CMA patients (n = 78; 16- to 30-year-old females and 17.5- to 30-year-old males) were evaluated prospectively for BMD using a DXA scan, serum values of bone turnover factor, and dietary and lifestyle questionnaires. Patients receiving > 2 short courses of systemic steroid treatments were excluded. RESULTS: Abnormal BMD measurements (T- or Z-scores < -1.0) of the lumbar vertebrae, femoral neck, or hip were noted in 60 patients, while normal BMD values were present in 18 patients, despite similarly decreased calcium intakes between the groups (P = 0.92). Patients with abnormal BMD were more likely to be asthmatic (P = 0.014), have a lower weight z-score (P = 0.007), have a decreased percent caloric intake derived from fat (P = 0.01), and have an increased carbohydrate intake (P = 0.03), in comparison with the normal-BMD group. Serum values of bone turnover were similar between the groups. On multivariate regression analysis, only asthma significantly (P = 0.006) increased the risk for osteopenia and osteoporosis (OR 38.5, 95% CI 2.8-500). Fitting continuous z-scores into a regression model, both asthma and weight z-score were significant (adjusted r2  = 0.272). Asthma was significantly overrepresented in osteopenic and osteoporotic subpopulations while decreased weight only in patients with osteoporosis. CONCLUSIONS: In the context of a low calcium intake, asthma and weight are independent risk factors for decreased BMD in IgE-CMA patients.

Food allergy to previously tolerated foods: Course and patient characteristics.

BACKGROUND: The acquisition of food allergy (FA) to previously safely consumed basic food proteins is an unusual presentation of immunoglobulin E (IgE)-mediated allergic disease. OBJECTIVE: We sought to characterize patients who developed FA to previously tolerated foods (FA-PTF), including underlying reasons for and length of elimination diet of previously tolerated foods. METHODS: Patients (n = 30) with complaints consistent with FA to foods previously consumed safely were evaluated. Clinical history was obtained, and skin prick testing and graded oral food challenges (OFC) were performed. One fatal case of FA-PTF was reported by a physician. RESULTS: Twenty-two of 30 patients (ages 1.2-50 years) were diagnosed with FA-PTF by OFC to milk (n = 17), egg (n = 2), and peanuts (n = 3). One additional patient with FA-PTF had a fatal reaction to milk. Anaphylactic reactions were reported in 12 of these 23 FA-PT patients (52%); 8 experienced multiple episodes. Atopic dermatitis was diagnosed in 52% (12/23) of patients, 8 of 12 as severe; overall, 18 of 23 (78%) of patients had marked personal atopic background. Sixteen patients (70%) initiated an elimination diet, 12 of whom did so on advice from a health care provider, before the appearance of allergic symptoms. However, in 4 patients with FA-PTF, reactivity to the food protein emerged during uninterrupted consumption. CONCLUSION: Food allergy to previously tolerated foods primarily appears after an elimination diet in atopic patients. Anaphylactic reactions are common. Health care providers should consider these risks before recommending elimination diet of tolerated foods.