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Background: Hyper-IgE syndrome (HIES) constitutes a group of rare primary immunodeficiency disorders. The diagnosis relies on the National Institutes of Health (NIH) scoring system, incorporating clinical and laboratory data. Scores greater than or equal to 15 raise a strong suspicion of the disease. In an isolated Israeli population, Zinc Finger 341 deficiency, a subtype of HIES, has a carrier incidence of 1:20, but the prevalence of the clinical syndrome within this community remains unknown., Objective: To estimate the prevalence of potentially undiagnosed HIES cases within this population by using the NIH scoring criteria., Methods: This retrospective cohort study obtained requisite clinical and laboratory data for NIH score computation from the electronic medical records of Clalit Health Services for the isolated village under scrutiny in comparison to a neighboring village. Subsequently, clinical scores were assigned to each subject, enabling comparative analysis of suspected diagnosis rates between the 2 populations., Results: Among the 29,390 studied subjects, 12 had a documented diagnosis of HIES. All were in the study village, and none were from the control village (0.08% vs 0%, P < .01). Within the study village, 235 individuals (1.62%) had an NIH score greater than or equal to 15 and were suspected with having HIES almost doubled compared with the control group at 130 individuals (0.87%) (P < .001)., Conclusion: This is the first time the NIH clinical score system has been used for population screening. The significant disparity in the prevalence of suspected, undiagnosed cases between the study village and the control village strongly suggests the potential utility of this tool for preliminary screening., Competing Interests: Disclosures The authors have no conflicts of interest to report., (Copyright © 2024 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Immunoglobulin (Ig)E-mediated food allergy is a growing health problem affecting up to 10% of children. It is well-established that early introduction to peanuts and eggs from 4 months of age has a preventive effect. In contrast, there is no consensus about the effect of breastfeeding on food allergy development., Objective: To evaluate the effect of breastfeeding and cows' milk formula (CMF) feeding on the development of IgE-mediated food allergy., Methods: Infants in the Cow's Milk Early Exposure Trial were followed for 12 months. The cohort was divided according to parental feeding preferences for the first 2 months of life: group 1: exclusive breastfeeding (EBF); group 2: breastfeeding with at least 1 daily meal of CMF; and group 3: feeding with CMF only., Results: Among a total of 1989 infants, 1071 were on EBF (53.8%), 616 were breastfed with addition of CMF (31%), and 302 were fed with CMF only (15.2%), from birth. By 12 months, 43 infants developed an IgE-mediated food allergy (2.2%); 31 in the EBF group (2.9%), 12 in the breastfeeding and CMF combined group (1.9%), and none in the CMF feeding-only group (P = .002). Family atopic comorbidity did not affect the results., Conclusion: In this prospective cohort, breastfed infants developed significantly higher rates of IgE-mediated food allergy during the first year of life. Perhaps the mechanism is related to compounds ingested by the mother and secreted in the breastmilk. Future larger cohorts should validate these results and offer the lactating mother recommendations., Trial Registration: The COMEET study and its derivatives were approved by the Ethics Committee of Meir Medical Center, IRB number 011-16-MMC. It was registered at the National Institutes of Health Clinical Trials Registry: NCT02785679., (Copyright © 2023 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Cow's milk allergy (CMA) is a common food allergy among infants. Information regarding the best timing for first exposure to cow's milk formula (CMF) is controversial and more evidence is required. Few randomized control trials have tried to accurately assess the timing and preventive effect of exposure to CMF on small cohorts., Objective: This study assessed the association between early, continuing exposure to CMF on the basis of the parents' preferences and the development of immunoglobulin E (IgE)-mediated CMA in a large birth cohort., Methods: Newborns were prospectively recruited shortly before birth and divided into 2 groups according to parental feeding preference for the first 2 months of life: (1) exclusive breastfeeding (EBF); or (2) at least 1 meal of CMF (with or without breastfeeding) daily. Infants were followed up monthly until the age of 12 months., Results: Among 1992 infants participating in the study, 1073 (53.86%) were in the EBF group until 2 months of age. IgE-mediated CMA was confirmed in 0.85% (n = 17); all were in the EBF group. Within this group, the prevalence of IgE-mediated CMA was 1.58% compared with 0 in the other groups (relative risk, 29.98; P < .001). Post hoc analysis revealed IgE-mediated CMA prevalence of 0.7% in the per-protocol EBF group vs 3.27% among breastfed infants who were exposed to a small amount of CMF during the first 2 months of life. A family atopic background did not affect the results., Conclusion: Early, continuing exposure to CMF from birth has the potential to prevent the development of IgE-mediated CMA and should be encouraged. However, the exposure needs to be consistent because occasional exposure increases the risk of developing IgE-mediated CMA and should be avoided., (Copyright © 2022 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)