Continuous cow's milk protein ingestion during infancy may promote casein-specific IgG4 production.

Background: Early supplementation and subsequent discontinuation of cow's milk formula (CMF) may increase the risk of cow's milk allergy in breast-fed infants, but little is known about the relationship between continuous CMF ingestion and cow's milk protein-specific immunoglobulin production. Objective: This study aimed to clarify the aforesaid relationship in cow's milk-sensitized infants. Methods: Using data from a randomized controlled trial of a Japanese birth cohort, we performed a subgroup analysis of participants who had ingested CMF in the first 3 days of life and exhibited a positive skin prick test response to cow's milk at age 6 months. We compared the differences in median titers of cow's milk-specific IgE, casein-specific IgE, and casein-specific IgG4 levels between participants who continued daily or intermittent CMF ingestion up to age 6 months (the "continuous group") and participants who discontinued CMF ingestion before age 6 months (the "discontinued group"). Results: From among 462 trial participants, 49 (10.6%) were included in this study (21 in the continuous group and 29 in the discontinued group). The median titer of cow's milk-specific IgE was 0.17 kUA/L (interquartile range [IQR] = <0.10 to 0.57) in the continuous group and 0.66 kUA/L (IQR = 0.49-1.18) in the discontinued group (P = .0008). The median titer of casein-specific IgE was <0.10 kUA/L (IQR = <0.10 to 0.15) in the continuous group and <0.10 kUA/L (IQR = <0.10 to 0.37) in the discontinued group (P = .51). The median titer of casein-specific IgG4 was 2.58 mgA/L (IQR = 0.77-6.73) in the continuous group and 0.09 mgA/L (IQR = 0.07-0.13) in the discontinued group (P < .0001). Conclusion: Continuous CMF ingestion may promote casein-specific IgG4 production in cow's milk-sensitized infants.

Differences in Characteristics Between Patients Who Met or Partly Met the Diagnostic Criteria for Food Protein-Induced Enterocolitis Syndrome (FPIES).

BACKGROUND: Some patients with food protein-induced enterocolitis (FPIES)-like allergy do not completely fulfill the diagnostic criteria of the international consensus guideline for FPIES. However, it is unclear whether such FPIES-like patients represent a completely different population from FPIES. OBJECTIVE: This study aimed to clarify differences in characteristics between patients with FPIES who fully met diagnostic criteria and those who partly met them. METHODS: This was a cross-sectional study using data at the time of registration in multicenter, prospective studies of patients with FPIES in Japan. Children who had delayed emesis within 1 to 4 hours and/or diarrhea within 5 to 10 hours after ingestion of food were recruited between March 2020 and February 2022. We examined their compatibility with the diagnostic criteria of the international consensus guideline and their detailed clinical characteristics, including trigger foods, the serving size that elicited symptoms, and antigen-specific IgE antibody titers. RESULTS: Of the 225 patients with FPIES, 140 fully met the diagnostic criteria whereas 79 patients did not fully meet them but demonstrated reproducible symptoms. The frequencies of pallor, lethargy, and diarrhea were significantly higher in those who met the criteria fully, whereas the age at onset, trigger foods, comorbidity, and perinatal information were comparable. Analysis of patients with FPIES to hen's egg revealed significantly higher levels of egg white- and egg yolk-specific IgE in patients who partly met criteria, whereas the serving size eliciting symptoms was comparable. CONCLUSIONS: Patients who partly met the diagnostic criteria may have a milder phenotype of FPIES, but this needs to be validated in further studies using biomarkers reflecting the pathophysiology.

Regular consumption following early introduction of allergenic foods and aggressive treatment of eczema are necessary for preventing the development of food allergy in children.

PURPOSE OF REVIEW: Over the past two decades, food allergy prevention strategies have shifted from 'delayed introduction' to 'no delayed introduction' to 'early introduction' of allergenic foods. This article reviews important research in this field published in the early 2020s to support future strategies for food allergy prevention. RECENT FINDINGS: Recent randomized controlled trials (RCTs), systematic reviews, meta-analyses, and real-world studies have reported that early allergenic food introduction, especially peanut and egg, are effective for preventing food allergies. However, there are also reports that food-induced anaphylaxis admission rates in infants are increasing. SUMMARY: Early allergenic food introduction by itself is not sufficient to prevent the development of food allergies. Recent RCTs (SPADE study and COMEET study) have demonstrated that continued regular cow's milk consumption after early introduction is important for preventing the onset of cow's milk allergy. Furthermore, an RCT (PACI study) reported that early and aggressive anti-inflammatory topical therapy for eczema can contribute to the prevention of egg allergy by suppressing percutaneous sensitization. Food allergies may be prevented through a combination of early food introduction, regular consumption, and active eczema treatment. Further research is needed to develop well tolerated, effective, and practical strategies to prevent food allergies.

Effects of regular soy formula intake between 1 and 2 months of age on food sensitization in infancy.

BACKGROUND: The effects of regular soy formula (SF) intake on the development of food sensitization in infancy remain unclear. This study aimed to assess the effects of regular SF intake between 1 and 2 months of age on food sensitization development by 6 months of age. METHODS: Using data from a randomized controlled trial of a birth cohort from four Japanese hospitals that assessed cow's milk allergy development, we performed a retrospective cohort study of 235 infants who avoided cow's milk formula and supplemented breastfeeding with SF as required between 1 and 2 months of age. Regular SF intake was defined as SF consumption of ≥14 days per month and ≥1350 ml per month. Food sensitization was defined as positive skin prick test reactions to hen's egg, cow's milk, wheat, and/or soy. Using multivariable logistic regression models that adjusted for parental, perinatal, and environmental factors, we calculated the adjusted odds ratios of regular SF intake for food, hen's egg, and cow's milk sensitization by 6 months of age. RESULTS: From the 235 participants, 114 (48.5%) had regular SF intake. The adjusted odds ratios of regular SF intake for food, hen's egg, and cow's milk sensitization were 0.32 (95% confidence interval: 0.16-0.62, p = .0007), 0.42 (0.20-0.88, p = .02), and 0.33 (0.14-0.81, p = .02), respectively. CONCLUSION: Regular SF intake between 1 and 2 months of age in infants avoiding cow's milk formula was significantly associated with a reduced risk of food sensitization in infancy.

Effects of delivery mode and labor duration on the development of food sensitization in infancy.

BACKGROUND: The effects of delivery mode and labor duration on the development of food sensitization (FS) in infancy remain unclear. OBJECTIVE: To elucidate the potential effects of delivery mode and labor duration on FS development by 6 months of age. METHODS: Using data from a randomized controlled trial of a birth cohort from 4 Japanese hospitals that assessed cow's milk allergy development by 6 months of age, we performed a nested case-control trial of 462 participants who had undergone the final assessment at 6 months of age. FS was defined as positive skin prick test reactions to hen's egg, cow's milk, wheat, or soy. For the primary outcome, we calculated the adjusted odds ratio of vaginal delivery (VD) relative to cesarean delivery for FS development by 6 months of age using a multivariable logistic regression analysis. For the secondary outcome, we compared labor durations between participants with and without FS using the Mann-Whitney U test. RESULTS: The adjusted odds ratio of VD for FS development was 2.54 (95% confidence interval, 1.32-4.87; P = .005). The median labor duration was significantly longer in participants with FS (5.7 hours, interquartile range, 2.7-10.1) than in participants without FS (4.5 hours, 1.1-8.2) (P = .01). CONCLUSION: VD was considerably associated with an increased risk of FS in infancy, and longer labor durations may promote FS development.

Early Discontinuation of Cow's Milk Protein Ingestion Is Associated with the Development of Cow's Milk Allergy.

BACKGROUND: Although early supplementation with cow's milk formula (CMF) reportedly increases the risk of cow's milk allergy (CMA) in breast-fed infants, little is known about the association between the timing of CMF discontinuation and subsequent CMA development. OBJECTIVE: To elucidate the relationship between the timing of CMF discontinuation and CMA development in infants who received CMF in the early days of life. METHODS: Using data from a randomized controlled trial of a birth cohort from 4 Japanese hospitals, we performed a subgroup analysis of participants who ingested CMF in the first 3 days of life. We compared the proportions of participants who developed CMA at age 6 months in those who discontinued CMF ingestion before age 1 month ("DISC <1-month group"), during age 1 to 2 months ("DISC 1-2-month group"), and during age 3 to 5 months ("DISC 3-5-month group") with those who continued CMF ingestion until age 6 months ("continuous group"). The risk ratios (RRs) and 95% CIs for CMA development were calculated. RESULTS: CMA incidence was significantly higher in the DISC <1-month group (n = 7 of 17, 41.2%; RR, 65.7; 95% CI, 14.7-292.5; P < .001), DISC 1-2-month group (n = 3 of 26, 11.5%; RR, 18.4; 95% CI, 3.2-105.3; P = .003), and DISC 3-5-month group (n = 7 of 69, 10.1%; RR, 16.2; 95% CI, 3.4-76.2; P < .001) than in the continuous group (n = 2 of 319, 0.6%). CONCLUSIONS: Early CMF discontinuation, particularly in the first month of life, was associated with CMA development in infants who received CMF in the first 3 days of life.

Randomized trial of early infant formula introduction to prevent cow's milk allergy.

BACKGROUND: Previous research has produced conflicting evidence on the preventive effects of early introduction of cow's milk protein on cow's milk allergy (CMA). OBJECTIVE: Through a randomized controlled trial, we sought to determine whether the early introduction of cow's milk formula (CMF) could serve as an effective strategy in the primary prevention of CMA in a general population. METHODS: We recruited newborns from 4 hospitals in Okinawa, Japan. Participants were randomly allocated to ingest at least10 mL of CMF daily (ingestion group) or avoid CMF (avoidance group) between 1 and 2 months of age. In the avoidance group breast-feeding was supplemented with soy formula as needed. Oral food challenge was performed at 6 months of age to assess CMA development. Continuous breast-feeding was recommended for both groups until 6 months of age. RESULTS: We identified 504 infants for randomization into the 2 groups. In all, the parents of 12 participants declined to receive the intervention, and the study sample comprised 491 participants (242 in the ingestion group and 249 in the avoidance group) for a modified intention-to-treat analysis. There were 2 CMA cases (0.8%) among the 242 members of the ingestion group and 17 CMA cases (6.8%) among the 249 participants in the avoidance group (risk ratio = 0.12; 95% CI = 0.01-0.50; P < .001). The risk difference was 6.0% (95% CI = 2.7-9.3). Approximately 70% of the participants in both groups were still being breast-fed at 6 months of age. CONCLUSIONS: Daily ingestion of CMF between 1 and 2 months of age prevents CMA development. This strategy does not compete with breast-feeding.

The ingestion of cow's milk formula in the first 3 months of life prevents the development of cow's milk allergy.

BACKGROUND: IgE-mediated cow's milk allergy (CMA) is one of the most common food allergies in infants. It is still controversial whether the early introduction of cow's milk formula (CMF) prevents the development of CMA. OBJECTIVE: We aimed to evaluate the duration and frequency of CMF ingestion as compere with exclusive breast-fed for preventing CMA in high-risk infants. METHODS: We enrolled the patients diagnosed with hen's egg allergy by an oral food challenge. A questionnaire was completed by the caregivers of the patients regarding the timing of introduction and discontinuation of CMF, and the frequency of CMF ingestion. Based on the information, we analyzed the relationship between the duration and frequency of CMF ingestion and the development of CMA at 3-24 months of age. RESULTS: Three hundred seventy-four patients were analyzed; 171 were diagnosed with CMA (45.7%). The analyzed patients (n = 374) were categorized into the following subgroups: exclusively breast-fed (breast-fed group, n = 75); discontinued ingestion of CMF before 3 months of age (temporary group, n = 177); continuous ingestion of CMF, but not daily, up to 3 months of age (nondaily group, n = 47); continuous ingestion of CMF at least once daily (daily group, n = 75). The incidence of developing CMA between the breast-fed group and temporary group did not show any statistical difference. Nondaily group and daily group had significantly lower incidence of developing CMA in comparison to the breast-fed group (nondaily group odds ratio 0.43; p = 0.02, daily group odds ratio 0.11; p < 0.001). CONCLUSION: Ingestion of CMF during the first 3 months of life might prevent the development of CMA in high-risk infants.